External validation of the Ruptured Arteriovenous Malformation Grading Scale (RAGS) in a multicenter adult cohort.

PURPOSE: While Ruptured Arteriovenous Malformation Grading Scale (RAGS) has recently been validated in children, the literature lacks validation on adults exclusively. Therefore, we aimed to determine the validity of RAGS on the external multicenter adult cohort and compare its accuracy with other scales. METHODS: A retrospective analysis was performed in five neurosurgical departments to extract patients who presented with the first episode of acute brain arteriovenous malformation (bAVM) rupture between 2012 and 2019. Standard logistic regression and area under the receiver operating curve (AUROC) calculations were performed to determine the value of the following scales: intracerebral hemorrhage (ICH), AVM-associated ICH (AVICH), Spetzler-Martin (SM), Supplemented SM (Supp-SM), Hunt and Hess (HH), Glasgow Coma Scale (GCS), World Federation of Neurological Surgeons (WFNS), and RAGS to predict change in categorical and dichotomized modified Rankin Scale (mRS) across three follow-up periods: within the 6 months, 6 months to 1 year, and above 1 year. RESULTS: Sixty-one individuals with a mean age of 43.6 years were included. The RAGS outperformed other grading scales during all follow-up time frames. It showed AUROC of 0.78, 0.74, and 0.71 at the first 6 months, between 6 and 12 months, and after 12 months of follow-up, respectively, when categorized mRS was applied, while corresponding values were 0.79, 0.76, and 0.73 for dichotomized mRS, respectively. CONCLUSION: The RAGS constitutes a reliable scale predicting clinical outcomes following bAVM rupture among adults. Furthermore, the RAGS proved its generalizability across medical centers with varying treatment preferences.

Combinatory Treatment with miR-7-5p and Drug-Loaded Cubosomes Effectively Impairs Cancer Cells.

BACKGROUND: Multidrug resistance (MDR) is an emerging problem in the treatment of cancer. Therefore, there is a necessity for novel strategies that would sensitize tumor cells to the administered chemotherapeutics. One of the innovative approaches in fighting drug-resistant tumors is the treatment of cancer with microRNA (miRNA), or the use of cubosomes (lipid nanoparticles) loaded with drugs. Here, we present a study on a novel approach, which combines both tools. METHODS: Cubosomes loaded with miR-7-5p and chemotherapeutics were developed. The effects of drug- and miRNA-loaded vehicles on glioma- (A172, T98G), papillary thyroid- (TPC-1) and cervical carcinoma-derived (HeLa) cells were analyzed using molecular biology techniques, including quantitative real-time PCR, MTS-based cell proliferation test, flow cytometry and spheroids formation assay. RESULTS: The obtained data indicate that miR-7-5p increases the sensitivity of the tested cells to the drug, and that nanoparticles loaded with both miRNA and the drug produce a greater anti-tumor effect in comparison to the free drug treatment. It was found that an increased level of apoptosis in the drug/miRNA co-treated cells is accompanied by an alternation in the expression of the genes encoding for key MDR proteins of the ABC family. CONCLUSIONS: Overall, co-administration of miR-7-5p with a chemotherapeutic can be considered a promising strategy, leading to reduced MDR and the induction of apoptosis in cancer cells.

Clinical Prognosis for SAH Consistent with Redox Imbalance and Lipid Peroxidation.

Subarachnoid hemorrhage (SAH) accounts for 3% of all strokes. As more and more data indicates the role of oxidative stress in acute brain damage caused by SAH, an attempt was made to correlate the clinical status of patients with systemic level of antioxidants and lipid peroxidation products. The hemorrhage was diagnosed with brain computed tomography (CT) and aneurysm with angio-CT and angiography, while the vasospasm was monitored with transcranial Doppler. Plasma glutathione peroxidase activity (GSH-Px) and vitamin A, E, and C levels were determined spectrophotometrically and by HPLC, respectively. The levels of polyunsaturated fatty acids (PUFAs) cyclization products were determined by GC-MS, while F2-isoprostanes and neuroprostanes (NP) were determined by LC-MS. SAH was accompanied by changes in antioxidant capacity in blood plasma, including initially (day 1) an increase in GSH-Px activity, followed by its decrease and a progressive decrease in glutathione (GSH) levels and vitamins A, E, and C. On the other hand, levels of PUFAs cyclization products, F2-isoprostanes, and neuroprostanes were highest on day 1 (two and eight times higher, respectively) and decreased over time. The levels of 4-HNE (4-hydroxynonenal), 4-ONE (4-oxononenal), and MDA (malondialdehyde) changed similarly. In contrast, the 4-HHE (4-hydroxyhexenal) level reduced after SAH increased significantly after a week. It was found that the deterioration of the overall clinical and neurological condition of SAH patients due to cerebral edema, intracranial hemorrhage, or vasoconstriction corresponded to reduced antioxidant defense and, as a consequence, increased lipid peroxidation and slower observed changes in regression. It can be concluded that monitoring the level of lipid peroxidation products (neuroprostanes, 4-ONE, and MDA) can support the monitoring of the clinical status of patients, especially with regard to the assessment of vasospasm.

Serum and cerebrospinal fluid Neudesin concentration and Neudesin Quotient as potential circulating biomarkers of a primary brain tumor.

BACKGROUND: Despite the previously suggested role of Neudesin in tumorigenesis and its potential as a novel target for the treatment of cancers, its prognostic value has never been examined. Thus, the aim of the study was to evaluate Neudesin concentrations in primary brain tumor patients and make a comparison with non-tumoral individuals. METHODS: Cerebrospinal fluid (CSF) and serum Neudesin concentration was evaluated by means of the ELISA method. RESULTS: The total group of brain tumor patients had statistically lower serum Neudesin concentrations compared to the non-tumoral group (P = 0.037). The meningeal tumor subgroup also had statistically lower serum Neudesin concentrations compared to the non-tumoral group (P = 0.012). The Astrocytic brain tumor subgroup had significantly higher CSF Neudesin concentrations compared to the non-tumoral group (P = 0.046). Neudesin Quotient (CSF concentration divided by serum concentration) in the astrocytic brain tumor subgroup was statistically higher compared to the non-tumoral group (P = 0.023). Males had statistically lower concentrations of the serum Neudesin compared to females (P = 0.047). Univariate linear regression analysis revealed that for women the serum Neudesin concentration was 1.53 times higher than for men. In the model of multivariate linear regression analysis, predictor variables influencing serum Neudesin concentrations included CSF Neudesin concentration and the Neudesin Quotient, if other model parameters are fixed. The developed model explains 82% of the variance in serum Neudesin concentration. Both linear regression models, univariate and multivariate, pointed to fewer factors with a potential to influence the Neudesin Quotient compared to serum Neudesin concentration. CONCLUSIONS: In astrocytic brain tumor patients Neudesin concentrations within the cerebrospinal fluid are higher compared with non-tumoral individuals. Serum Neudesin concentration strongly correlates with its CSF level. In primary brain tumor patients serum Neudesin concentration is clearly gender-dependent. Linear regression models pointed to fewer factors that may influence the Neudesin Quotient value, which suggests it is a better biomarker of astrocytic brain tumors than serum and CSF Neudesin concentrations alone.

Biomechanical evaluation of single- and multi-level anterior cervical discectomy and fusion with polyetheretherketone cages: radiological and clinical outcomes.

OBJECTIVE: The aim of this study was to analyse the outcomes of single- and multi-level anterior cervical discectomy and fusion (ACDF) with standalone polyetheretherketone (PEEK) cages, with particular emphasis on the risk of secondary adjacent segment disease. MATERIALS AND METHODS: This retrospective study included 30 patients with single- or multi-level cervical disc herniation. Before the ACDF, and one year thereafter, the patients underwent clinical and radiological evaluation including determination of cervical pain severity with a numerical rating scale (NRS), and a survey with a Polish adaptation of the neck disability index questionnaire (NDI-PL). Biomechanical parameters of the cervical spine were determined using the Cobb method. RESULTS: One year after ACDF, all patients had achieved complete fusions, and 97% showed a significant reduction of pain severity. Also, a significant decrease in all NDI-PL indices was observed. A significant decrease in overall cervical spine mobility coexisted with a significant increase in the mobility of the segment above the one operated upon and a non-significant decrease in the mobility of the segment below. No statistically significant change was found in the intervertebral disc space height (IVH) above and below the operated segment, and no evidence of degeneration within the segments adjacent to the operated one was documented. CONCLUSION: One- and two-level ACDF with standalone PEEK cages provided high fusion rates. Surgical spondylosis contributed to a reduction of spinal mobility despite the hypermobility in adjacent spinal segments. No degeneration in adjacent spinal segments was documented within a year of ACDF, and the treatment seemed to improve patients' quality of life.

Expression of N-cadherin and ß-catenin in human meningioma in correlation with peritumoral edema.

OBJECTIVE: To analyze the expression of ß-catenin and N-cadherin in large series of meningioma cases and to investigate their correlation with peritumoral brain edema (PTBE). MATERIALS AND METHODS: Study group consists of 154 patients diagnosed with intracranial meningioma divided into: low-grade (G1) and high-grade (G2 or G3) group. PTBE was graded into four groups (0, I, II, III) using Steinhoff classification. The expression of N-cadherin, ß-catenin was analyzed and graded based on the positive ratio of immunoreactivity. The results were analyzed statistically. RESULTS: 104 cases were low-grade and 50 high-grade meningiomas. PTBE was observed in 103(66.8 %) cases: 57 grade I, 44 grade II and 2 grade III. Positive N-cadherin expression was found only in the membrane of the neoplastic cells in 50(48.1%) cases of low-grade, and in 34(68%) of high-grade group. In low-grade meningioma, ß-catenin expression was observed within the cytoplasm and nucleus in 54(51.9%) cases. In high-grade meningiomas, ß-catenin expression was observed in 33(66%) tumors only within the nucleus. N-cadherin expression was observed in 36 cases with PTBE grade I, 28 with grade II and 2 with grade III. ß-catenin expression was observed in 40 cases with PTBE grade I, 24 with grade II and 2 with grade III. The results were statistically significant. CONCLUSIONS: Significant N-cadherin expression especially in high-grade meningioma group was found. ß-catenin expression was the most evident in the nucleus rather than in cytoplasm. The degree of PTBE correlated with the N-cadherin and ß-catenin expression and was the most prominent in high-grade meningioma group.

Late ophthalmological manifestations in patients with subarachnoid hemorrhage and coiling of cerebral aneurysm.

Late ocular manifestations of aneurysmal subarachnoid hemorrhage (SAH) have not been previously investigated except for one study which demonstrated that one half of patients subjected to aneurysm clipping suffer from symptoms of visual pathway impairment. We assessed ophthalmological status of patients after 1-4.5 years from SAH and aneurysm embolization to identify predictors of damage to the visual pathways. Complete ophthalmological examination, static perimetry, and visual evoked potentials (VEPs) were performed in 74 patients (26 men, 48 women, aged 19-76 years), who constituted a consecutive sample of 129 patients treated with aneurysm embolization in the years 2008-2010. The following independent variables: sex, age, time from SAH to embolization, size and site of aneurysm, score in Glasgow Coma Scale, Glasgow Outcome Scale, Hunt-Hess and Fisher scales were subject to univariate and multivariate statistical analyses to study their influence on the ocular outcome. 40 patients (54%) demonstrated visual field defects appearing as multiple peripheral foci and constricted field, affecting both eyes. Among these subjects, 12 patients had severe defects in the visual field, 20 had deterioration in VEPs, and 9 had decreased visual acuity. Older age and high score in Hunt-Hess and Fisher scales were identified as predictors for visual field defects and disturbances in VEPs. More than half of the survivors of SAH and aneurysm embolization suffer from a permanent defect in visual function. Damage of visual pathway correlates with severity of SAH and older age of patients.

[Evaluation of the effectiveness of endovascular embolization for the treatment of ruptured cerebral aneurysms]. / Ocena skutecznosci embolizacji wewnatrznaczyniowej w leczeniu peknietych tetniaków mózgu.

Endovascular embolization of ruptured intracranial aneurysms is a relatively new and still developing technique, therefore its efficiency and risks should be assessed recurrently, including also results obtained in national centers. AIM: The aim of the study was to present a synthetic review of the literature, which, including the data published by the Polish centers, typify the global assessment of the effectiveness and early complication of endovascular embolization in patients with ruptured brain aneurysms. MATERIALS AND METHODS: Our review of the literature includes 24 papers listed in PubMed and Medline, including also two Polish case series. The following data were extracted from the publications and compiled into global characteristics of a case series: basic characteristic of the study group, neurological status on admission, feasibility of procedure, incidence of complications and their type, outcome at discharge and intraoperative morbidity and mortality. RESULTS: Effective embolization was feasible in 94.4% of patients. Total occlusion of the cerebral aneurysm (99-100%) during initial procedure was achieved in 60.7% of patients. Intraoperative complications occurred in 12.6% of individuals. The most frequent type of intraoperative complication was thromboembolism, which occurred in 6%. As much as 65.2% of patients scored 4 or 5 in GOS on discharge. CONCLUSIONS: Endovascular embolization is highly effective in the treatment of ruptured cerebral aneurysms, featured also by a low rate of intra-procedural complications. The majority of patients are discharged in good shape and neurological status, scoring 4-5 in GOS.

Early outcomes and perioperative complications of endovascular embolization in patients with aneurysmal SAH.

BACKGROUND: We still lack reliable data on the outcomes of endovascular coiling for ruptured cerebral aneurysms. As this is still an evolving technique, the outcomes of the procedures performed in the past and more recently cannot be directly compared. We present the early outcomes of endovascular coiling in a relatively large group of patients with ruptured intracranial aneurysms. METHOD: The study included 190 consecutive patients (a total of 216 aneurysms) subjected to endovascular coiling in 2006-2013 (127 women aged 56±13 years and 63 men aged 50± 15 years). Up to 87.5% of the aneurysms were located within anterior circulation. Most patients presented with "mild to moderate" subarachnoid hemorrhages (85% of Hunt &Hess scores 1-3, and 72% of Fisher scores 1-3). RESULTS: Embolization was feasible in 176 (92.6%) patients. In 14 cases, the embolization was not attainable due to unfavorable anatomy of the aneurysm, intraoperative vasospasm and/or aneurysm rupture, or prolapse of a coil. Early complications related to the procedure were recorded in 23 (13.1%) patients. The most common perioperative complication was aneurysm rupture. All fatal complications occurred in patients with aneurysms located at the anterior circle of Willis. At the time of discharge, 126 patients scored 4 or 5 on the Glasgow Outcome Scale. CONCLUSIONS: Endovascular embolization is an effective and relatively safe method for treatment of ruptured cerebral aneurysms. Complications related to the procedure are significantly less frequent in the case of vertebral-basilar complex aneurysms.

The transmaxillary endoscopic approach to the inferior part of the orbit: how I do it.

BACKGROUND: Transmaxillary endoscopic approach to the inferior part of the orbit was demonstrated on cadaveric preparations; however, its clinical application has not been reported. We describe a clinically useful technique of the transmaxillary approach to the lower orbit. METHODS: A four-hand technique is essential for extensive preparation within the orbit; therefore, the tools have to be introduced into the maxillary sinus through two ports: either through the canine fossa and antrostomy or through antrostomy using the bi-nostril transseptal approach. CONCLUSION: Intraorbital pathologies located in the inferior retrobulbar space can be successfully operated on using the transmaxillary endoscopic approach.

The interaction of bee products with temozolomide in human diffuse astrocytoma, glioblastoma multiforme and astroglia cell lines.

In the present study, we investigated the influence of extracts from Salix spp. honey (ESH), beebread (EBB), and royal jelly (ERJ) with and without temozolomide (TMZ) on cell lines derived from a patient with diffuse astrocytoma (DASC), human glioblastoma multiforme (U87MG), and normal human astroglia (SVGp12). DASC was identified by immunocytochemistry. TMZ (20 µM) in combination with ESH (30 µg/mL), EBB (50 µg/mL), and ERJ (30 µg/mL) has stronger cytotoxic activity on U87MG cells after 72 h (20.0, 26.5, and 29.3% of control, respectively) than TMZ alone (about 6% of control). An increase of the cytotoxic effect and inhibition of DNA synthesis in SVGp12 were detected after administering TMZ with the studied extracts. NF-κB p50 subunit was reduced in U87MG cells after treatment with ESH (70.9%) and ESH + TMZ (74.7%). A significant decline of MMP-9 and MMP-2 secretion in cultured U87MG was detected after incubation with EBB (42.9% and 73.0%, respectively) and EBB + TMZ (38.4% and 68.5%, respectively). In conclusion, the use of bee products may increase the cytotoxic effect of TMZ in U87MG but also in SVGp12 cell line. It is important to note that the U87MG cells were sensitive to natural bee products, although there was no influence of natural bee products on the DASC cells.

Dietary habits and selenium, glutathione peroxidase and total antioxidant status in the serum of patients with relapsing-remitting multiple sclerosis.

BACKGROUND: Dietary habits and adequate dietary intake of antioxidants in the diet may be one of the most important environmental factors for the prevention of Multiple Sclerosis (MS). OBJECTIVES: The aim of this study was to estimate selenium (Se) concentration, glutathione peroxidase (GSH-Px) activity and total antioxidant status (TAS) in the serum of patients with MS and the influence of dietary habits on the status. METHODS: 101 patients with relapsing-remitting MS (aged 18-58 years), as well as control group of 63 healthy people (aged 19-65 years) were studied. Food-frequency questionnaires were implemented to collect the dietary data. Se concentration in the serum samples was determined by atomic absorption spectrometry. GSH-Px activity and TAS in examined serum was measured using the ready-made sets of tests by Randox Laboratories Ltd., UK. RESULTS: Serum Se concentration and GSH-Px activity in the serum of patients with MS (55.2±16.2 µg/L, 6676.1±2386.4 U/L; respectively) were significantly decreased (p<0.01, p<0.05; respectively) compared with control group (79.2±20.6 µg/L, 8029.9±2650.1 U/L; respectively). A significant correlation (r=0.39, p<0.01) was observed between Se concentration and GSH-Px activity in the serum of examined patients. TAS value in the serum of patients with MS (1.03±0.37 mmol/L) was also significantly lower (p<0.01) than in healthy volunteers (1.48±0.41 mmol/L). Frequent consumption of poultry, bakery products, pulses and fish seemed to increase serum Se concentration in the group of patients; whereas frequent consumption of butter, wholegrain bread, sweet beverages and sugar was found to accompany with lower values of Se in the serum. We have observed significant decrease TAS (p<0.05, p<0.01; respectively) in the serum of smokers and those patients who received immunomodulatory drugs (0.95±0.39 mmol/L, 0.92±0.34 mmol/L; respectively) compared with no-smoking patients and not taking immunomodulators (1.14±0.33 mmol/L, 1.31±0.31 mmol/L; respectively). CONCLUSIONS: Serum Se concentration, GSH-Px activity and TAS value were significantly lower in patients with relapsing-remitting MS compared with healthy volunteers. Dietary habits have a significant influence on Se status. Smoking cigarettes and intake of immunomodulatory drugs therapy have a negative impact on TAS of examined patients.

Endoscopic lateral orbitotomy.

BACKGROUND: Lateral orbitotomy can be minimalized using contemporary endoscopy. METHODS: Anatomy of the temporal fossa/orbital wall junction is described. The attachment of the temporal fascia is cut off from the orbital rim through a 1.5 cm skin incision in the lateral orbital wrinkle. The temporal muscle is detached from the bone to create a space for the telescope. An appropriate bone opening in the lateral orbital wall is created with the aid of neuronavigation to handle intraorbital pathology. CONCLUSION: Endoscopic lateral orbitotomy is an original alternative to the microsurgical Krönlein approach and yields good functional and cosmetic results.

Endoscopic drainage of orbital abscesses aided with intraoperative sonography.

BACKGROUND AND PURPOSE: Accurate localization and adequate visualization of the superiorly or inferiorly located subperiosteal orbital abscesses or intraorbital abscess is difficult with transnasal endoscopic approach. Sonography is a well-known and effective tool for evaluation of orbital pathologies but no paper documenting intraoperative application of this method in orbital abscess surgery has been published to date. MATERIAL AND METHODS: We present a series of 12 patients in whom orbital abscesses were drained endoscopically with an aid of neuronavigation and intraoperative ultrasonography. The abscesses were localized subperiosteally in the medial (n=6), superior (n=2) or inferior (n=1) part of the orbit whereas in 3 patients the abscess was localized in the intraconal space. RESULTS: According to intraoperative sonographic imaging complete drainage of the abscess was achieved in 11 out of 12 patients and no complications occurred. Intraoperative sonography helped to limit opening of the orbital wall in the medial subperiosteal abscesses, enabled check-up for completeness of drainage of the far extending pouches in the superior and inferior subperiosteal abscesses and enabled visualization of the tip of surgical instrument when reaching deeply located intraorbital abscesses. CONCLUSIONS: Intraoperative ultrasonography facilitates the endoscopic management of orbital abscesses, especially those which are difficult to reach due to subperiosteal location in the superior and inferior parts of the orbit, or abscesses localized intraorbitally.

Endoscopic transconjunctival surgical approach to intraconal space of the orbit: first clinical experience.

BACKGROUND AND PURPOSE: Recently, a transconjunctival, endoscope-assisted (TEA) approach to the medial intra-orbital space was developed based on cadaver preparations, with an ultimate goal of minimizing disturbances of the anatomic structures of the orbit. However, no report on clinical validation of this promising technique was published thus far. We present our experiences with the TEA approach in two patients. MATERIAL AND METHODS: In emergency conditions, we approached the lateral retrobulbar space of a 42-year-old male through a 180° incision close to the corneal limbus; a scrap of metal, which had perforated the globe and resided at its posterior wall, was removed endoscopically. Moreover, we used the TEA approach to remove a tumor from the upper intraconal space in a 63-year-old woman. RESULTS: In both patients the surgical goal was achieved with no muscle transection and without additional morbidity and complications. CONCLUSIONS: Our experiences with TEA approach suggest that the procedure is clinically feasible, produces no co-morbidity and yields good functional and cosmetic results. As a result, the whole circumference of the retrobulbar space can be conveniently explored.

Blood flow velocity in the middle cerebral artery during transnasal endoscopic skull base surgery performed in controlled hypotension.

BACKGROUND AND PURPOSE: To assess blood flow velocity in the middle cerebral artery (MCA) during transnasal endoscopic procedures performed with decreased hemodynamic parameters. MATERIALS AND METHODS: In 40 patients who underwent endoscopic skull base surgery in controlled hypotension (studied group) and in 13 patients operated without reduction of hemodynamic parameters (control group), blood flow velocity in MCA was assessed with transcranial color Doppler sonography. RESULTS: Blood flow velocity in MCA remained within the range of age-specific reference values in all patients before operation. It decreased significantly in both groups after induction of anesthesia and then dropped even further in studied group of patients when hemodynamic parameters were reduced; the systolic velocity fell below the normal reference values in 25% of patients, the mean velocity in 50% and the diastolic velocity in 57% of patients. The diastolic velocity was much more heavily influenced by diminished hemodynamic parameters than systolic velocity in the studied group as opposed to the control group where reduction of blood flow velocity pertained equally systolic and diastolic velocity. CONCLUSION: During transnasal endoscopic procedures performed in moderate hypotension, in addition to significant drop of blood flow velocity to values well below the normal reference range, a divergent reduction of systolic and diastolic velocity was detected. Since divergent systolic and diastolic velocity may indicate an early phase of cerebral autoregulation compromise, and the decrease of mean blood flow velocity in MCA corresponds with a decrease of cerebral blood flow, further investigations in this field seem warranted.

Early Intraocular Complications of Subarachnoid Haemorrhage after Aneurysm Rupture.

The aim of this study was to identify factors predisposing for early intraocular complications of aneurysmal subarachnoid haemorrhage (SAH). The authors analysed 96 selected cases of aneurysmal SAH. Forty patients (42%) demonstrated abnormal fundus findings, including disc swelling (13.5%), retinal haemorrhages (23%), and vitreous haemorrhage (5%). The incidence of intraocular pathologies was significantly higher in patients who lost consciousness at the onset of SAH, were admitted with high scores of the Hunt-Hess and Fisher scales and low score of the Glasgow Coma Scale, as well as in those with arterial hypertension, more sizable aneurysm, and older.

Planned Subtotal Resection following Stereotactic Radiosurgery of Koos 3 and 4 Vestibular Schwannomas.

Background/Objectives: Surgical resection of medium to large vestibular schwannomas (VSs, Koos grade 3 and 4) is a widely used approach, although stereotactic radiosurgery (SRS) is increasingly proposed as initial treatment. The quality of life-centered approach is challenged in cases where tumor growth control cannot be achieved with SRS, thus necessitating salvage surgery. We present a series of eight consecutive patients who required surgery due to continued tumor growth after SRS. Methods: Of the 146 patients with VS grades 3 and 4 initially treated with SRS, only eight patients (mean age, 54 ± 7.2 years; range, 42-63 years) required subsequent surgery. Their mean tumor volume was 9.9 ± 3.2 cm3. The mean time from SRS to first tumor progression and planned subtotal resection was 23 ± 5.9 months and 45 ± 17.5 months, respectively. SRS was not performed after the surgery in favor of a "wait and rescan" approach. Tumor residue was monitored on follow-up magnetic resonance imaging. In all patients, tumor growth control after planned subtotal resection was maintained at 63 ± 19.8 months. Results: None of the 146 patients had serious complications after SRS. In the eight patients who required surgery, tumor growth between 22% and 212% (mean, 4 cm3) was reported within 26 to 84 months after SRS. Before salvage surgery, they scored 1 point on the House-Brackmann scale. Subtotal excision was performed, and VIIth nerve function was preserved in all patients. At 63 ± 19.8 months, 3 patients had a House-Brackmann score of 1, four patients had a score of 2, and one patient had a score of 3. Conclusions: Surgical excision of medium to large VS after SRS can be relatively safe, provided that a quality of life-centered approach of subtotal resection is used.

Circulating serum miR-362-3p and miR-6721-5p as potential biomarkers for classification patients with adult-type diffuse glioma.

According to the fifth edition of the WHO Classification of Tumours of the Central Nervous System (CNS) published in 2021, grade 4 gliomas classification includes IDH-mutant astrocytomas and wild-type IDH glioblastomas. Unfortunately, despite precision oncology development, the prognosis for patients with grade 4 glioma remains poor, indicating an urgent need for better diagnostic and therapeutic strategies. Circulating miRNAs besides being important regulators of cancer development could serve as promising diagnostic biomarkers for patients with grade 4 glioma. Here, we propose a two-miRNA miR-362-3p and miR-6721-5p screening signature for serum for non-invasive classification of identified glioma cases into the highest-grade 4 and lower-grade gliomas. A total of 102 samples were included in this study, comprising 78 grade 4 glioma cases and 24 grade 2-3 glioma subjects. Using the NanoString platform, seven miRNAs were identified as differentially expressed (DE), which was subsequently confirmed via RT-qPCR analysis. Next, numerous combinations of DE miRNAs were employed to develop classification models. The dual panel of miR-362-3p and miR-6721-5p displayed the highest diagnostic value to differentiate grade 4 patients and lower grade cases with an AUC of 0.867. Additionally, this signature also had a high AUC = 0.854 in the verification cohorts by RT-qPCR and an AUC = 0.842 using external data from the GEO public database. The functional annotation analyses of predicted DE miRNA target genes showed their primary involvement in the STAT3 and HIF-1 signalling pathways and the signalling pathway of pluripotency of stem cells and glioblastoma-related pathways. For additional exploration of miRNA expression patterns correlated with glioma, we performed the Weighted Gene-Co Expression Network Analysis (WGCNA). We showed that the modules most associated with glioma grade contained as many as six DE miRNAs. In conclusion, this study presents the first evidence of serum miRNA expression profiling in adult-type diffuse glioma using a classification based on the WHO 2021 guidelines. We expect that the discovered dual miR-362-3p and miR-6721-5p signatures have the potential to be utilised for grading gliomas in clinical applications.

Evaluation of mast cells and hypoxia inducible factor-1 expression in meningiomas of various grades in correlation with peritumoral brain edema.

Meningiomas are common primary brain tumors. However, they are often complicated by significant peritumoral brain edema, which leads to surgery difficulties and prolonged hospitalization. The aim of this study was to evaluate the presence of mast cells and expression of hypoxia inducible factor-1 (HIF-1) in correlation with the grade of meningioma and presence of peritumoral brain edema. Immunohistochemistry was performed with specific antibodies against tryptase (mast cells) and HIF-1 in low grade meningiomas (estimated as G1) and high grade meningiomas (estimated as G2 or G3). Peritumoral brain edema observed in MRI was graded using Steinhoff classification. Tryptase expression was observed in 40.4 % low grade meningiomas and in 90 % high grade cases; HIF-1 in 55.7 % low grade and in 84 % high grade meningiomas. There was a statistically significant correlation between HIF-1 and tryptase expression in both groups (p = 0.003). Presence of peritumoral brain edema statistically correlated with tryptase (p = 0.001) and HIF-1 expression (p = 0.004). Mast cells as well as hypoxia are involved in meningioma progression, and may be associated with the formation of peritumoral brain edema leading to surgery complication and recovery. Therefore, they may be useful markers in predicting the clinical course of meningioma cases.