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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.
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Neoplasias Encefálicas , Progresión de la Enfermedad , Glioblastoma , Metionina , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/diagnóstico , Radioisótopos de Carbono , Glioblastoma/diagnóstico por imagen , Glioblastoma/terapia , Glioblastoma/diagnóstico , Glioblastoma/radioterapia , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Estudios Prospectivos , Radiofármacos/uso terapéutico , Planificación de la Radioterapia Asistida por Computador/métodosRESUMEN
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.
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Neoplasias Meníngeas , Meningioma , Humanos , Femenino , Anciano , Meningioma/cirugía , Meningioma/patología , Neoplasias Meníngeas/cirugía , Recurrencia Local de Neoplasia/cirugía , Microcirugia , Resultado del Tratamiento , Estudios Retrospectivos , Procedimientos Neuroquirúrgicos/métodosRESUMEN
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.
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Arteria Pulmonar , Humanos , Masculino , Arteria Pulmonar/cirugía , Migración de Cuerpo Extraño/cirugía , Migración de Cuerpo Extraño/diagnóstico por imagen , Derivaciones del Líquido Cefalorraquídeo/efectos adversos , Atrios Cardíacos/cirugía , AdultoRESUMEN
Background: The aim of this retrospective study is to analyze a consecutive cohort of brain metastasis (BM) patients treated off clinical trials through combination of surgery and radiotherapy over the last 15 years in a tertiary neurooncology center. Materials and methods: All BM patients operated between 2007-2019 received adjuvant linac-based radiotherapy categorized to whole brain radiotherapy (WBRT) and tumor bed stereotactic radiotherapy. Survival outcomes and local control was analyzed. Results: In total, 118 patients were enrolled, those with stereotactic radiotherapy (41%) had better baseline characteristics mirrored in longer overall survival (OS) [18 vs. 7.1 months, p < 0.001; hazard ratio (HR) 0.47, p = 0.004] with median follow-up of 58 months. Cumulative incidence for local, distant, and extracranial control was not significantly different between groups, with 12-month cumulative control of 22% vs. 18%, 44% vs. 29%, and 35% vs. 32% for stereotactic and WBRT group, respectively. WBRT was an independent factor for better distal brain control. Conclusions: Real world data demonstrating significantly better overall survival in patients treated with postoperative targeted radiotherapy compared with postoperative WBRT is presented, with no significant difference in cumulative incidence for local or distant brain control. The majority of patients with targeted radiotherapy had a fractionated dose schedule with outcomes comparable to single-dose radiation trials of postoperative targeted radiotherapy.
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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.
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Fusión Vertebral , Estenosis Espinal , Espondilolistesis , Humanos , Descompresión Quirúrgica/métodos , Espondilolistesis/complicaciones , Espondilolistesis/cirugía , Vértebras Lumbares/cirugía , Fusión Vertebral/métodos , Dolor , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
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.
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Lesiones Encefálicas , Enfermedades del Sistema Inmune , Humanos , Lesiones Encefálicas/complicaciones , Escala de Coma de Glasgow , Biomarcadores , Enfermedades del Sistema Inmune/complicacionesRESUMEN
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.
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Infartos del Tronco Encefálico/cirugía , Cerebelo/cirugía , Procedimientos Neuroquirúrgicos/efectos adversos , Procedimientos Neuroquirúrgicos/métodos , Infartos del Tronco Encefálico/diagnóstico por imagen , Cerebelo/irrigación sanguínea , Cerebelo/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos/tendencias , Factores de RiesgoRESUMEN
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.
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Embolización Terapéutica , Malformaciones Arteriovenosas Intracraneales , Humanos , Malformaciones Arteriovenosas Intracraneales/cirugía , Microcirugia , Investigación , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
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.
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Inflamación/microbiología , Degeneración del Disco Intervertebral/microbiología , Factores de Crecimiento Nervioso/genética , Propionibacterium acnes/fisiología , Adulto , Células Cultivadas , Femenino , Interacciones Huésped-Patógeno , Humanos , Inflamación/genética , Interleucina-1beta/genética , Disco Intervertebral/metabolismo , Disco Intervertebral/microbiología , Degeneración del Disco Intervertebral/genética , Masculino , Persona de Mediana Edad , Regulación hacia ArribaRESUMEN
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.
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Antibacterianos/farmacocinética , Cefazolina/farmacocinética , Clindamicina/farmacocinética , Infecciones por Bacterias Grampositivas/prevención & control , Degeneración del Disco Intervertebral/cirugía , Desplazamiento del Disco Intervertebral/cirugía , Disco Intervertebral/metabolismo , Propionibacterium acnes , Vancomicina/farmacocinética , Adulto , Antibacterianos/uso terapéutico , Cefazolina/uso terapéutico , Clindamicina/uso terapéutico , Humanos , Vancomicina/uso terapéuticoRESUMEN
Unfortunately, the complete conflict of interest statement was missed out in the original publication. The same is given below.
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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.
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Antioxidantes/administración & dosificación , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/dietoterapia , Demencia/prevención & control , Vitamina E/análogos & derivados , Vitamina E/administración & dosificación , Animales , Lesiones Traumáticas del Encéfalo/psicología , Demencia/etiología , Suplementos Dietéticos , HumanosRESUMEN
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.
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Glioma/genética , ARN Largo no Codificante/genética , Animales , Biomarcadores de Tumor/genética , Glioma/patología , Humanos , Patología Molecular , PronósticoRESUMEN
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.
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Hemorragia Cerebral/cirugía , Descompresión Quirúrgica/efectos adversos , Aneurisma Intracraneal/cirugía , Complicaciones Posoperatorias/epidemiología , Adulto , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/etiología , Femenino , Humanos , Aneurisma Intracraneal/complicaciones , Aneurisma Intracraneal/diagnóstico por imagen , Masculino , Persona de Mediana EdadRESUMEN
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.
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Neoplasias Encefálicas/patología , Daño del ADN/genética , Regulación Neoplásica de la Expresión Génica/genética , Glioblastoma/patología , MicroARNs/genética , Proteínas de Neoplasias/biosíntesis , ARN Neoplásico/genética , Tolerancia a Radiación/genética , Neoplasias Encefálicas/genética , Proteínas Portadoras/biosíntesis , Proteínas Portadoras/genética , Puntos de Control del Ciclo Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de la radiación , División Celular/efectos de los fármacos , División Celular/efectos de la radiación , Línea Celular Tumoral , Femenino , Perfilación de la Expresión Génica , Glioblastoma/genética , Humanos , Masculino , Proteínas de la Membrana/biosíntesis , Proteínas de la Membrana/genética , Persona de Mediana Edad , Proteínas de Unión al GTP Monoméricas/biosíntesis , Proteínas de Unión al GTP Monoméricas/genética , Proteínas de Neoplasias/genética , Neuropéptidos/biosíntesis , Neuropéptidos/genética , Proteína Fosfatasa 2/biosíntesis , Proteína Fosfatasa 2/genética , Proteína Homóloga de Ras Enriquecida en el CerebroRESUMEN
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.
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Biomarcadores de Tumor/genética , Neoplasias Encefálicas/genética , Proliferación Celular , Perfilación de la Expresión Génica , Glioblastoma/genética , MicroARNs/genética , Algoritmos , Encéfalo/metabolismo , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Metilación de ADN , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Estudios de Seguimiento , Glioblastoma/mortalidad , Glioblastoma/patología , Humanos , Estadificación de Neoplasias , Pronóstico , Regiones Promotoras Genéticas/genética , Estudios Retrospectivos , Tasa de Supervivencia , Proteínas Supresoras de Tumor/genéticaRESUMEN
OBJECTIVE: Ischemic complications account for significant patient morbidity following aneurysmal subarachnoid hemorrhage (aSAH). The Prevention and Treatment of Vasospasm with Clazosentan (REACT) study was designed to assess the safety and efficacy of clazosentan, an endothelin receptor antagonist, in preventing clinical deterioration due to delayed cerebral ischemia (DCI) in patients with aSAH. METHODS: REACT was a prospective, multicenter, randomized, double-blind, phase 3 study. Eligible patients had aSAH secured by surgical clipping or endovascular coiling, and had presented with thick and diffuse clot on admission CT scan. Patients were randomized (1:1 ratio) to 15 mg/hour intravenous clazosentan or placebo within 96 hours of the aSAH for up to 14 days, in addition to standard of care treatment including oral or intravenous nimodipine. The primary efficacy endpoint was the occurrence of clinical deterioration due to DCI up to 14 days after initiation of the study drug. The main secondary endpoint was the occurrence of clinically relevant cerebral infarction at day 16 after study drug initiation. Other secondary endpoints included clinical outcome assessed on the modified Rankin Scale (mRS) and the Glasgow Outcome Scale-Extended (GOSE) at week 12 post-aSAH. Imaging and clinical endpoints were centrally adjudicated. RESULTS: A total of 409 patients were randomized between February 2019 and May 2022 across 74 international sites. Three patients did not start study treatment and were not included in the analysis set. The occurrence of clinical deterioration due to DCI was 15.8% (32/202 patients) in the clazosentan group and 17.2% (35/204 patients) in the placebo group, and the difference was not statistically significant (relative risk reduction [RRR] 7.2%, 95% CI -42.6% to 39.6%, p = 0.734). A nonsignificant RRR of 34.1% (95% CI -21.3% to 64.2%, p = 0.177) was observed in clinically relevant cerebral infarcts treated with clazosentan (7.4%, 15/202) versus placebo (11.3%, 23/204). Rescue therapy was less frequently needed for patients treated with clazosentan compared to placebo (10.4%, 21/202 vs 18.1%, 37/204; RRR 42.6%, 95% CI 5.4%-65.2%). A nonsignificant relative risk increase of 25.4% (95% CI -10.7% to 76.0%, p = 0.198) was reported in the risk of poor GOSE and mRS scores with clazosentan (24.8%, 50/202) versus placebo (20.1%, 41/204) at week 12 post-aSAH. Treatment-emergent adverse events were similar to those reported previously. CONCLUSIONS: Clazosentan administered for up to 14 days at 15 mg/hour had no significant effect on the occurrence of clinical deterioration due to DCI. Clinical trial registration no.: NCT03585270 (ClinicalTrials.gov) EU clinical trial registration no.: 2018-000241-39 (clinicaltrialsregister.eu).
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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.
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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.
RESUMEN
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.