11C-methionine in the diagnostics and management of glioblastoma patients with rapid early progression: nonrandomized, open label, prospective clinical trial (GlioMET).

BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary brain cancer. The treatment of GBM consists of a combination of surgery and subsequent oncological therapy, i.e., radiotherapy, chemotherapy, or their combination. If postoperative oncological therapy involves irradiation, magnetic resonance imaging (MRI) is used for radiotherapy treatment planning. Unfortunately, in some cases, a very early worsening (progression) or return (recurrence) of the disease is observed several weeks after the surgery and is called rapid early progression (REP). Radiotherapy planning is currently based on MRI for target volumes definitions in many radiotherapy facilities. However, patients with REP may benefit from targeting radiotherapy with other imaging modalities. The purpose of the presented clinical trial is to evaluate the utility of 11C-methionine in optimizing radiotherapy for glioblastoma patients with REP. METHODS: This study is a nonrandomized, open-label, parallel-setting, prospective, monocentric clinical trial. The main aim of this study was to refine the diagnosis in patients with GBM with REP and to optimize subsequent radiotherapy planning. Glioblastoma patients who develop REP within approximately 6 weeks after surgery will undergo 11C-methionine positron emission tomography (PET/CT) examinations. Target volumes for radiotherapy are defined using both standard planning T1-weighted contrast-enhanced MRI and PET/CT. The primary outcome is progression-free survival defined using RANO criteria and compared to a historical cohort with REP treated without PET/CT optimization of radiotherapy. DISCUSSION: PET is one of the most modern methods of molecular imaging. 11C-Methionine is an example of a radiolabelled (carbon 11) amino acid commonly used in the diagnosis of brain tumors and in the evaluation of response to treatment. Optimized radiotherapy may also have the potential to cover those regions with a high risk of subsequent progression, which would not be identified using standard-of-care MRI for radiotherapy planning. This is one of the first study focused on radiotherapy optimization for subgroup of patinets with REP. TRIAL REGISTRATION: NCT05608395, registered on 8.11.2022 in clinicaltrials.gov; EudraCT Number: 2020-000640-64, registered on 26.5.2020 in clinicaltrialsregister.eu. Protocol ID: MOU-2020-01, version 3.2, date 18.09.2020.

Neurosurgical treatment and outcome patterns in patients with meningioma in South Moravian region-a population-based study.

INTRODUCTION: Meningiomas are usually slow-growing tumours, constituting about one third of all primary intracranial tumours. They occur more frequently in women. Clinical manifestation of meningiomas depends on their location, tumour size and growth rate. In most cases, surgical treatment is the procedure of choice. The success of this treatment is, however, associated with the radicality of the resection. Radiotherapy represents an additional or alternative treatment modality. Gamma knife surgery is another notable treatment method, especially in small and/or slow-growing tumours in eloquent areas or in elderly patients. MATERIAL AND METHODS: Authors describe their experience with the diagnosis, treatment and outcome of the patients with meningioma (n = 857). Furthermore, they also assess the postoperative morbidity/mortality and recurrence rate. RESULTS AND CONCLUSIONS: In view of the benign histology of meningiomas, the success of the treatment largely depends (besides the tumour grading) on the radicality of the resection. The emphasis is also put on appropriate follow-up of the patients. In certain patients, the watch and wait strategy should be also considered as a suitable treatment method.

Migration of atrial catheter of ventriculo-cysto-atrial shunt into heart and pulmonary artery - case report and literature review.

Ventriculoatrial shunts are the alternative treatments when it is impossible to use ventriculoperitoneal shunts. Limited indication for ventriculoatrial shunt is due to the possibility of very serious complications inherent with this procedure. We present a case report of a young patient who suffered from disconnection of an atrial catheter from the valve after an accidental blow to his neck. The atrial catheter was dislocated to the heart and pulmonary artery and it was extracted through the femoral vein in the groin area using an endovascular technique. The procedure went without complications. A new atrial catheter was introduced under ultrasonic guidance during surgical revision.

Decompression alone versus decompression with instrumented fusion in the treatment of lumbar degenerative spondylolisthesis: a systematic review and meta-analysis of randomised trials.

OBJECTIVE: To determine the efficacy of adding instrumented spinal fusion to decompression to treat degenerative spondylolisthesis (DS). DESIGN: Systematic review with meta-analysis. DATA SOURCES: MEDLINE, Embase, Emcare, Cochrane Library, CINAHL, Scopus, ProQuest Dissertations & Theses Global, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform from inception to May 2022. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised controlled trials (RCTs) comparing decompression with instrumented fusion to decompression alone in patients with DS. Two reviewers independently screened the studies, assessed the risk of bias and extracted data. We provide the Grading of Recommendations, Assessment, Development and Evaluation assessment of the certainty of evidence (COE). RESULTS: We identified 4514 records and included four trials with 523 participants. At a 2-year follow-up, adding fusion to decompression likely results in trivial difference in the Oswestry Disability Index (range 0-100, with higher values indicating greater impairment) with mean difference (MD) 0.86 (95% CI -4.53 to 6.26; moderate COE). Similar results were observed for back and leg pain measured on a scale of 0 to 100, with higher values indicating more severe pain. There was a slightly increased improvement in back pain (2-year follow-up) in the group without fusion shown by MD -5·92 points (95% CI -11.00 to -0.84; moderate COE). There was a trivial difference in leg pain between the groups, slightly favouring the one without fusion, with MD -1.25 points (95% CI -6.71 to 4.21; moderate COE). Our findings at 2-year follow-up suggest that omitting fusion may increase the reoperation rate slightly (OR 1.23; 0.70 to 2.17; low COE). CONCLUSIONS: Evidence suggests no benefits of adding instrumented fusion to decompression for treating DS. Isolated decompression seems sufficient for most patients. Further RCTs assessing spondylolisthesis stability are needed to determine which patients would benefit from fusion. PROSPERO REGISTRATION NUMBER: CRD42022308267.

Immune system disorders in the early post-injury period in patients after severe brain injury from the perspective of the severity of the injury.

BACKGROUND: Brain injuries are the most common cause of death in productive age. Besides the extent of the injury, other systemic factors can also affect the outcome. Patients suffering from severe brain injury often experience extracranial inflammatory complications during the early period of treatment. Here, we investigate the changes in immunity in patients with brain injury. METHODS: 121 patients and 92 healthy controls were included in the research. Blood samples were collected on admission and analyzed by flow cytometry and biochemical methods. Multiple clusters of differentiation (CD) and antibody levels were investigated. The results were compared between patients and controls. In addition, results of two classes of severity (Glasgow Coma Scale, GCS, of 3-5 vs. 6-8) were also compared. RESULTS: Parameters of humoral immunity in patients immediately after admission were significantly lower than those from healthy donors, with the exception of IgE elevated as much as to resemble allergic reaction (p < 0.01). Of cellular parameters, only natural killer (NK) cluster CD56 + was elevated (p < 0.01). Extracranial infectious complications were more common in patients with GCS 3-5. CONCLUSIONS: Strong immune system disorders were observed in patients after severe brain injury, which may contribute to the worse outcome in such patients.

What is the risk of venous cerebellar infarction in the supracerebellar infratentorial approach?

The supracerebellar infratentorial approach (SCITA) is a standard approach used in a neurosurgical practice. It carries some risk of associated complications including cerebellar venous infarction with possible serious sequelae. The objective of this study is to address the incidence of cerebellar venous infarction in SCITA. A search through the currently available literature was performed in September 2019 from the year 2000 until September 2019 dealing with 'supracerebellar infratentorial approach'. Out of the 578 patients found in thirteen case series, two venous infarctions were present; the remaining four patients were published as case reports. By analysing the case series, we calculated the risk of such a complication to be 0.345% (95% CI [0.061%, 1.248%]). Case reports were not included. The real risk is estimated to be higher. The risk of cerebellar venous infarction is an unpredictable, infrequent but real complication with potentially dreadful sequelae. Each neurosurgeon using this approach should be aware of this event when employing this approach. The avoidance of cerebellar venous infarction can be lowered by leaving as many bridging veins intact as possible.

The efficacy of surgical treatment of cerebral arteriovenous malformations in a single academic institution: a case series.

AIM: To report on patients who underwent surgical treatment of arteriovenous malformations (AVMs) at our institution. METHODS: This retrospective single-center case series enrolled the patients who underwent surgical treatment of pial AVM at the Department of Neurosurgery, University Hospital Brno, between 2005 and 2019. The data are summarized as descriptive statistics presenting basic characteristics in all the patients and in sex or age subgroups. RESULTS: Fifty patients were enrolled. The majority of AVMs were of Spetzler-Martin grade II (n=27; 54%), localized supratentorialy (n=43; 86%), and half of AVMs were ruptured. A total resection was performed in 48 patients (96%), and a good overall outcome was achieved in 44 patients (88%). Surgery-associated morbidity was 2%, and the mortality rate was 0% due to meticulous selection of patients for surgical treatment. CONCLUSION: Microsurgery is an appropriate method of treatment for S-M grade I-III pial AVMs. Microsurgery may be used to treat the majority of small-nidus AVMs with a low mortality and morbidity, when precisely planned and performed by an expert vascular team. The meticulous selection of patients for surgical treatment is crucial.

Pro-Inflammatory and Neurotrophic Factor Responses of Cells Derived from Degenerative Human Intervertebral Discs to the Opportunistic Pathogen Cutibacterium acnes.

Previously, we proposed the hypothesis that similarities in the inflammatory response observed in acne vulgaris and degenerative disc disease (DDD), especially the central role of interleukin (IL)-1ß, may be further evidence of the role of the anaerobic bacterium Cutibacterium (previously Propionibacterium) acnes in the underlying aetiology of disc degeneration. To investigate this, we examined the upregulation of IL-1ß, and other known IL-1ß-induced inflammatory markers and neurotrophic factors, from nucleus-pulposus-derived disc cells infected in vitro with C. acnes for up to 48 h. Upon infection, significant upregulation of IL-1ß, alongside IL-6, IL-8, chemokine (C-C motif) ligand 3 (CCL3), chemokine (C-C motif) ligand 4 (CCL4), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), was observed with cells isolated from the degenerative discs of eight patients versus non-infected controls. Expression levels did, however, depend on gene target, multiplicity and period of infection and, notably, donor response. Pre-treatment of cells with clindamycin prior to infection significantly reduced the production of pro-inflammatory mediators. This study confirms that C. acnes can stimulate the expression of IL-1ß and other host molecules previously associated with pathological changes in disc tissue, including neo-innervation. While still controversial, the role of C. acnes in DDD remains biologically credible, and its ability to cause disease likely reflects a combination of factors, particularly individualised response to infection.

Intervertebral disc penetration by antibiotics used prophylactically in spinal surgery: implications for the current standards and treatment of disc infections.

PURPOSE: The presence of Propionibacterium acnes in a substantial component of resected disc specimens obtained from patients undergoing discectomy or microdiscectomy has led to the suggestion that this prominent human skin and oral commensal may exacerbate the pathology of degenerative disc disease. This hypothesis, therefore, raises the exciting possibility that antibiotics could play an important role in treating this debilitating condition. To date, however, little information about antibiotic penetration into the intervertebral disc is available. METHODS: Intervertebral disc tissue obtained from 54 microdiscectomy patients given prophylactic cefazolin (n = 25), clindamycin (n = 17) or vancomycin (n = 12) was assayed by high-performance liquid chromatography, with cefaclor as an internal standard, to determine the concentration of antibiotic penetrating into the disc tissue. RESULTS: Intervertebral disc tissues from patients receiving the positively charged antibiotic clindamycin contained a significantly greater percentage of the antibacterial dose than the tissue from patients receiving negatively charged cefazolin (P < 0.0001) and vancomycin, which has a slight positive charge (P < 0.0001). CONCLUSION: Positively charged antibiotics appear more appropriate for future studies investigating potential options for the treatment of low-virulence disc infections. These slides can be retrieved under Electronic Supplementary Material.

Correction to: Intervertebral disc penetration by antibiotics used prophylactically in spinal surgery: implications for the current standards and treatment of disc infections.

Unfortunately, the complete conflict of interest statement was missed out in the original publication. The same is given below.

Therapeutic potential of vitamin E and its derivatives in traumatic brain injury-associated dementia.

Traumatic brain injury is one of the most common causes for intervention in neurosurgery. Apart from its acute consequence, it can represent a further burden on individuals as well as society by being associated with significant comorbidity-mainly early-onset dementia. Oxidative stress is one of the crucial mechanisms conferring the damage to nervous tissue, and it is believed it could be, to some extent, influenced by dietary composition, largely by antioxidants contained in the diet. Under stressful conditions, cell-derived reactive oxygen species in the brain can induce the formation of lipid peroxides and the shifting of redox homeostasis. This review discusses the potential of vitamin E as a potent antioxidant and its derived molecules, including vitamin E-based lazaroids, in traumatic brain injury, summarizing the current state of knowledge of its role in TBI-associated dementia.

Long Non-Coding RNAs in Gliomas: From Molecular Pathology to Diagnostic Biomarkers and Therapeutic Targets.

Gliomas are the most common malignancies of the central nervous system. Because of tumor localization and the biological behavior of tumor cells, gliomas are characterized by very poor prognosis. Despite significant efforts that have gone into glioma research in recent years, the therapeutic efficacy of available treatment options is still limited, and only a few clinically usable diagnostic biomarkers are available. More and more studies suggest non-coding RNAs to be promising diagnostic biomarkers and therapeutic targets in many cancers, including gliomas. One of the largest groups of these molecules is long non-coding RNAs (lncRNAs). LncRNAs show promising potential because of their unique tissue expression patterns and regulatory functions in cancer cells. Understanding the role of lncRNAs in gliomas may lead to discovery of the novel molecular mechanisms behind glioma biological features. It may also enable development of new solutions to overcome the greatest obstacles in therapy of glioma patients. In this review, we summarize the current knowledge about lncRNAs and their involvement in the molecular pathology of gliomas. A conclusion follows that these RNAs show great potential to serve as powerful diagnostic, prognostic, and predictive biomarkers as well as therapeutic targets.

Middle cerebral artery aneurysms with intracerebral hematoma-the impact of side and volume on final outcome.

BACKGROUND: Middle cerebral artery aneurysms (MCA aneurysms) belong to the most frequent type of intracranial aneurysms forming an intracerebral hematoma. The consequences of the hematoma-the laterality, the impact of ICH volume and size of the aneurysm with the final outcome of these patients had not been studied in detail in this location, and we focused on the analysis of these factors. METHODS: Patients with MCA aneurysms and associated intracerebral hematomas with a volume ≥10 ml were studied; these were treated from January 2006 to December 2015. During this period, more than 700 patients with spontaneous subarachnoid hemorrhage were admitted to the Department of Neurosurgery, University Hospital Brno. The data were collected from the subarachnoid hemorrhage database of the unit and from the local hospital registry. All consecutive patients at the treating center were involved in this retrospective study. We collected clinical data such as age, gender, aneurysm location, preoperative hematoma size, Hunt-Hess grade and type of surgical procedures. We focused on the analysis of the final outcome [Glasgow Outcome Scale (GOS) score] in relation to ICH volume, side of bleeding and finally the relationship between aneurysm size and the volume of ICH. RESULTS: Fifty-eight patients with an MCA aneurysm and ICH were included; the mean age of this series was 59.4 years. Thirty-six patients (62%) had clinical status Hunt-Hess 4-5 on admission. The mean size of the intracerebral hematoma was 47.1 ml (10-133 ml). Most frequently, in 30 patients (52%), the hematoma had bled into the temporal lobe. Fifty three patients were operated on, and 5 were treated conservatively because of their poor condition. Twenty-three patients (40%) had a favorable Glasgow Outcome Scale score, and 35 (60%) had an unfavorable outcome including 20 patients (35%) who died. Of the 53 patients operated on, 20 (38%) underwent decompressive hemicraniectomy (DHC). Patients with an unfavorable outcome had significantly larger hematomas with a median size of 54 ml, whereas those with a favorable outcome had a median size of 26 ml (p = 0.0022). Larger hematomas were found on the right side. The cutoff volume for an unfavorable outcome in ICH was 25 ml. The outcomes were not related to the side of the ICH (p = 0.42), and the aneurysm size did not predetermine the ICH volume (p = 0.3159). CONCLUSION: Our study confirms the benefit of the active treatment of patients with MCA aneurysms and associated ICH. A significant proportion of these patients achieves a favorable outcome. No association between the side of bleeding and outcome was demonstrated. Hematomas larger than 25 ml have a greater tendency to lead to an unfavorable outcome. The treatment decision-making process should not differ for either side.

MiR-338-5p sensitizes glioblastoma cells to radiation through regulation of genes involved in DNA damage response.

Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor. Despite radical surgery and radiotherapy supported by chemotherapy, the disease still remains incurable with an extremely low median survival rate of 12-15 months from the time of initial diagnosis. The main cause of treatment failure is considered to be the presence of cells that are resistant to the treatment. MicroRNAs (miRNAs) as regulators of gene expression are involved in the tumor pathogenesis, including GBM. MiR-338 is a brain-specific miRNA which has been described to target pathways involved in proliferation and differentiation. In our study, miR-338-3p and miR-338-5p were differentially expressed in GBM tissue in comparison to non-tumor brain tissue. Overexpression of miR-338-3p with miRNA mimic did not show any changes in proliferation rates in GBM cell lines (A172, T98G, U87MG). On the other hand, pre-miR-338-5p notably decreased proliferation and caused cell cycle arrest. Since radiation is currently the main treatment modality in GBM, we combined overexpression of pre-miR-338-5p with radiation, which led to significantly decreased cell proliferation, increased cell cycle arrest, and apoptosis in comparison to irradiation-only cells. To better elucidate the mechanism of action, we performed gene expression profiling analysis that revealed targets of miR-338-5p being Ndfip1, Rheb, and ppp2R5a. These genes have been described to be involved in DNA damage response, proliferation, and cell cycle regulation. To our knowledge, this is the first study to describe the role of miR-338-5p in GBM and its potential to improve the sensitivity of GBM to radiation.

Risk Score based on microRNA expression signature is independent prognostic classifier of glioblastoma patients.

Glioblastoma multiforme (GBM) is the most malignant primary brain tumor. The prognosis of GBM patients varies considerably and the histopathological examination is not sufficient for individual risk estimation. MicroRNAs (miRNAs) are small, non-coding RNAs that function as post-transcriptional regulators of gene expression and were repeatedly proved to play important roles in pathogenesis of GBM. In our study, we performed global miRNA expression profiling of 58 glioblastoma tissue samples obtained during surgical resections and 10 non-tumor brain tissues. The subsequent analysis revealed 28 significantly deregulated miRNAs in GBM tissue, which were able to precisely classify all examined samples. Correlation with clinical data led to identification of six-miRNA signature significantly associated with progression free survival [hazard ratio (HR) 1.98, 95% confidence interval (CI) 1.33-2.94, P < 0.001] and overa+ll survival (HR 2.86, 95% CI 1.91-4.29, P < 0.001). O(6)-methylguanine-DNA methyltransferase methylation status was evaluated as reference method and Risk Score based on six-miRNA signature indicated significant superiority in prediction of clinical outcome in GBM patients. Multivariate Cox analysis indicated that the Risk Score based on six-miRNA signature is an independent prognostic classifier of GBM patients. We suggest that the Risk Score presents promising prognostic algorithm with potential for individualized treatment decisions in clinical management of GBM patients.

Open Microsurgical Cerebral Aneurysm Treatment After Failed Endovascular Therapy: An Evaluation of Aneurysm Treatment Frequencies in All Neurovascular Centers Across Austria and the Czech Republic Over 20 Years.

BACKGROUND AND OBJECTIVES: Endovascular treatment of cerebral aneurysms has tremendously advanced over the past decades. Nevertheless, aneurysm residual and recurrence remain challenges after embolization. The objective of this study was to elucidate the portion of embolized aneurysms requiring open surgery and evaluate whether newer endovascular treatments have changed the need for open surgery after failed embolization. METHODS: All 15 cerebrovascular centers in Austria and the Czech Republic provided overall aneurysm treatment frequency data and retrospectively reviewed consecutive cerebral aneurysms treated with open surgical treatment after failure of embolization from 2000 to 2022. All endovascular modalities were included. RESULTS: On average, 1362 aneurysms were treated annually in the 2 countries. The incidence increased from 0.006% in 2005 to 0.008% in 2020 in the overall population. Open surgery after failed endovascular intervention was necessary in 128 aneurysms (0.8%), a proportion that remained constant over time. Subarachnoid hemorrhage was the initial presentation in 70.3% of aneurysms. The most common location was the anterior communicating artery region (40.6%), followed by the middle cerebral artery (25.0%). The median diameter was 6 mm (2-32). Initial endovascular treatment included coiling (107 aneurysms), balloon-assist (10), stent-assist (4), intrasaccular device (3), flow diversion (2), and others (2). Complete occlusion after initial embolization was recorded in 40.6%. Seventy-one percent of aneurysms were operated within 3 years after embolization. In 7%, the indication for surgery was (re-)rupture and, in 88.3%, reperfusion. Device removal was performed in 16.4%. Symptomatic intraoperative and postoperative complications occurred in 10.2%. Complete aneurysm occlusion after open surgery was achieved in 94%. CONCLUSION: Open surgery remains a rare indication for cerebral aneurysms after failed endovascular embolization even in the age of novel endovascular technology, such as flow diverters and intrasaccular devices. Regardless, it is mostly performed for ruptured aneurysms initially treated with primary coiling that are in the anterior circulation.

Brain Tissue Oxygen Levels as a Perspective Therapeutic Target in Traumatic Brain Injury. Retrospective Cohort Study.

Introduction: Management of traumatic brain injury (TBI) requires a multidisciplinary approach and represents a significant challenge for both neurosurgeons and intensivists. The role of brain tissue oxygenation (PbtO2) monitoring and its impact on posttraumatic outcomes remains a controversial topic. Aim of the study: Our study aimed to evaluate the impact of PbtO2 monitoring on mortality, 30 days and 6 months neurological outcomes in patients with severe TBI compared with those resulting from standard intracranial pressure (ICP) monitoring. Material and methods: In this retrospective cohort study, we analysed the outcomes of 77 patients with severe TBI who met the inclusion criteria. These patients were divided into two groups, including 37 patients who were managed with ICP and PbtO2 monitoring protocols and 40 patients who were managed using ICP protocols alone. Results: There were no significant differences in demographic data between the two groups. We found no statistically significant differences in mortality or Glasgow Outcome Scale (GOS) scores one month after TBI. However, our results revealed that GOS scores at 6 months had improved significantly among patients managed with PbtO2; this finding was particularly notable for Glasgow Outcome Scale (GOS) scores of 4-5. Close monitoring and management of reductions in PbtO2, particularly by increasing the fraction of inspired oxygen, was associated with higher partial pressures of oxygen in this group. Conclusions: Monitoring of PbtO2 may facilitate the appropriate evaluation and treatment of low PbtO2 and represents a promising tool for the management of patients with severe TBI. Additional studies will be needed to confirm these findings.

Epidural Hematoma, a Rare Complication After the Use of Mayfield Clamp: A Case Report and Review of the Literature.

Herein, we describe a case of epidural hematoma associated with the use of a Mayfield head clamp. An 18-year old patient with an upper brainstem tumour causing obstructive hydrocephalus underwent a routine third ventriculostomy, which unexpectedly revealed an intracranial hemorrhage. We outline potential risk factors, propose an algorithm for preventing complications associated with the use of pin-type fixation, and conducted a structured review of the literature to identify similar clinical scenarios.

Effects of goal-directed fluid management guided by a non-invasive device on the incidence of postoperative complications in neurosurgery: a pilot and feasibility randomized controlled trial.

BACKGROUND: The positive effects of goal-directed hemodynamic therapy (GDHT) on patient-orientated outcomes have been demonstrated in various clinical scenarios; however, the effects of fluid management in neurosurgery remain unclear. Therefore, this study was aimed at assessing the safety and feasibility of GDHT using non-invasive hemodynamic monitoring in elective neurosurgery. The incidence of postoperative complications was compared between GDHT and control groups. METHODS: We conducted a single-center randomized pilot study with an enrollment target of 34 adult patients scheduled for elective neurosurgery. We randomly assigned the patients equally into control and GDHT groups. The control group received standard therapy during surgery and postoperatively, whereas the GDHT group received therapy guided by an algorithm based on non-invasive hemodynamic monitoring. In the GDHT group, we aimed to achieve and sustain an optimal cardiac index by using non-invasive hemodynamic monitoring and bolus administration of colloids and vasoactive drugs. The number of patients with adverse events, feasibility criteria, perioperative parameters, and incidence of postoperative complications was compared between groups. RESULTS: We successfully achieved all feasibility criteria. The GDHT protocol was safe, because no patients in either group had unsatisfactory brain tissue relaxation after surgery or brain edema requiring therapy during surgery or 24 h after surgery. Major complications occurred in two (11.8%) patients in the GDHT group and six (35.3%) patients in the control group (p = 0.105). CONCLUSIONS: Our results suggested that a large randomized trial evaluating the effects of GDHT on the incidence of postoperative complications in elective neurosurgery should be safe and feasible. The rate of postoperative complications was comparable between groups. TRIAL REGISTRATION: Trial registration: ClininalTrials.gov, registration number: NCT04754295, date of registration: February 15, 2021.

Effects of Reoperation Timing on Survival among Recurrent Glioblastoma Patients: A Retrospective Multicentric Descriptive Study.

Glioblastoma inevitably recurs, but no standard regimen has been established for treating this recurrent disease. Several reports claim that reoperative surgery can improve survival, but the effects of reoperation timing on survival have rarely been investigated. We, therefore, evaluated the relationship between reoperation timing and survival in recurrent GBM. A consecutive cohort of unselected patients (real-world data) from three neuro-oncology cancer centers was analyzed (a total of 109 patients). All patients underwent initial maximal safe resection followed by treatment according to the Stupp protocol. Those meeting the following criteria during progression were indicated for reoperation and were further analyzed in this study: (1) The tumor volume increased by >20-30% or a tumor was rediscovered after radiological disappearance; (2) The patient's clinical status was satisfactory (KS ≥ 70% and PS WHO ≤ gr. 2); (3) The tumor was localized without multifocality; (4) The minimum expected tumor volume reduction was above 80%. A univariate Cox regression analysis of postsurgical survival (PSS) revealed a statistically significant effect of reoperation on PSS from a threshold of 16 months after the first surgery. Cox regression models that stratified the Karnofsky score with age adjustment confirmed a statistically significant improvement in PSS for time-to-progression (TTP) thresholds of 22 and 24 months. The patient groups exhibiting the first recurrence at 22 and 24 months had better survival rates than those exhibiting earlier recurrences. For the 22-month group, the HR was 0.5 with a 95% CI of (0.27, 0.96) and a p-value of 0.036. For the 24-month group, the HR was 0.5 with a 95% CI of (0.25, 0.96) and a p-value of 0.039. Patients with the longest survival were also the best candidates for repeated surgery. Later recurrence of glioblastoma was associated with higher survival rates after reoperation.