Preoperative Immune-Inflammatory Status of the Patients With Newly-Diagnosed Glioblastoma - Could It Genuinely Predict Their Survival?

BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive brain tumor affecting adult patients, with an extremely reduced overall survival despite rapid diagnosis and treatment. Therefore, it is crucial to establish accurate and affordable markers that allow an individualized approach to GBM patients. Serum biomarkers could be the most accessible, as complete blood counts should be performed on all GBM patients before undergoing any surgical and/or pharmacological treatment. However, their prognostic role is still unclear. Our study aims to assess the influence of various hematological markers of inflammation in predicting the outcome of GBM patients. MATERIAL AND METHODS: We retrospectively analyzed all adult patients diagnosed with primary glioblastoma in the Neurosurgery Department of the Emergency Clinical County Hospital of Târgu Mureș, Romania, from January 2017 until December 2019. We aimed to discover whether the immune/inflammatory status of the patients before receiving any kind of pharmacological or surgical treatment influenced their overall survival. RESULTS: Our study showed that pre-therapeutic elevated white blood count could predict reduced overall survival in not otherwise specified subtype (NOS) of GBMs (HR 0.4153, 95% CI 0.1825-0.9449, p 0.0362). Furthermore, patients with increased systemic immune response index (SIRI) had much larger tumors at the time of diagnosis (p 0.0359). In wild type, isocitrate dehydrogenase subpopulation (IDHwt), the higher values of neutrophil-to-lymphocyte ratio (NLR, p 0.0412), platelet-to-lymphocyte ratio (PLR, p 0.0376) and monocyte-to-lymphocyte ratio (MLR, p 0.0412) were related to more advanced age at the moment of diagnosis. Moreover, our results revealed a weakly positive association between tumor size and NLR values in the NOS group (Spearman r 0.3212, p 0.0493). CONCLUSIONS: Our study does not provide enough evidence for the immune/inflammatory status of GBM patients to be used as an efficient prognostic marker to guide the therapeutic approach.

The Role of Ketone Bodies in Treatment Individualization of Glioblastoma Patients.

Glioblastoma is the most common and aggressive primary brain tumor in adults. According to the 2021 WHO CNS, glioblastoma is assigned to the IDH wild-type classification, fulfilling the specific characteristic histopathology. We have conducted a prospective observational study to identify the glucose levels, ketone bodies, and the glucose-ketone index in three groups of subjects: two tumoral groups of patients with histopathological confirmation of glioblastoma (9 male patients, 7 female patients, mean age 55.6 years old) or grade 4 astrocytoma (4 male patients, 2 female patients, mean age 48.1 years old) and a control group (13 male patients, 9 female patients, mean age 53.9 years old) consisting of subjects with no personal pathological history. There were statistically significant differences between the mean values of glycemia (p value = 0.0003), ketones (p value = 0.0061), and glucose-ketone index (p value = 0.008) between the groups of patients. Mortality at 3 months in glioblastoma patients was 0% if the ketone levels were below 0.2 mM and 100% if ketones were over 0.5 mM. Patients with grade 4 astrocytoma and the control subjects all presented with ketone values of less than 0.2 mM and 0.0% mortality. In conclusion, highlighting new biomarkers which are more feasible to determine such as ketones or glucose-ketone index represents an essential step toward personalized medicine and survival prolongation in patients suffering from glioblastoma and grade 4 astrocytoma.

Oxidative Stress in Amyotrophic Lateral Sclerosis: Synergy of Genetic and Environmental Factors.

Amyotrophic lateral sclerosis (ALS) is a grievous neurodegenerative disease whose survival is limited to only a few years. In spite of intensive research to discover the underlying mechanisms, the results are fairly inconclusive. Multiple hypotheses have been regarded, including genetic, molecular, and cellular processes. Notably, oxidative stress has been demonstrated to play a crucial role in ALS pathogenesis. In addition to already recognized and exhaustively studied genetic mutations involved in oxidative stress production, exposure to various environmental factors (e.g., electromagnetic fields, solvents, pesticides, heavy metals) has been suggested to enhance oxidative damage. This review aims to describe the main processes influenced by the most frequent genetic mutations and environmental factors concurring in oxidative stress occurrence in ALS and the potential therapeutic molecules capable of diminishing the ALS related pro-oxidative status.

Ischemic Stroke in Patients with Cancer: a Retrospective Cross-Sectional Study.

INTRODUCTION: An increasing trend of cancer associated stroke has been noticed in the past decade. OBJECTIVES: To evaluate the risk factors and the incidence of neoplasia in stroke patients. MATERIAL AND METHOD: A retrospective, observational study was undertaken on 249 patients with stroke and active cancer (SAC) and 1563 patients with stroke without cancer (SWC). The general cardiovascular risk factors, the site of cancer, and the general clinical data were registered and evaluated. According to the "Oxfordshire Community Stroke Project" (OCSP) classification, all patients were classified into the clinical subtypes of stroke. The aetiology of stroke was considered as large-artery atherosclerosis, small vessel disease, cardio-embolic, cryptogenic or other determined cause. RESULTS: The severity of neurological deficits at admission were significantly higher in the SAC group (p<0.01). The haemoglobin level was significantly lower, and platelet level and erythrocyte sedimentation rate were significantly higher in the SAC group. Glycaemia, cholesterol and triglycerides levels were significantly higher in the SWC group. The personal history of hypertension was more frequent in the SWC group. In the SAC group, 28.9% had a cryptogenic aetiology, compared to 9.1% in SWC group. Cardio-embolic strokes were more frequent in the SAC group (24%) than the SWC group (19.6%). In the SAC group, 15,6% were diagnosed with cancer during the stroke hospitalization, and 78% of the SAC patients were without metastasis. CONCLUSIONS: The most frequent aetiologies of stroke in cancer patients were cryptogenic stroke, followed by large-artery atherosclerosis. SAC patients had more severe neurological deficits and worse clinical outcomes than SWC patients. Stroke in cancer patients appears to be more frequently cryptogenic, probably due to cancer associated thrombosis. The association between stroke and cancer is important, especially in stroke of cryptogenic mechanism, even in the presence of traditional cardiovascular risk factors.

Gross-total versus near-total resection of large vestibular schwannomas. An institutional experience.

OBJECTIVE: We will report our experience of the surgical treatment of large vestibular schwannomas (VSs). PATIENTS, MATERIALS AND METHODS: We conducted a retrospective study of patients operated on for Koos grade IV VS between 2007 and 2015 at the Department of Neurosurgery, Emergency County Hospital, Târgu Mures, Romania. We studied the general preoperatory clinical data, the preoperative and postoperative facial nerve status, preoperative hearing on the affected side, and any postoperative complications, including death. RESULTS: Sixty-six cases were included in our study. The mean age was 52.95 years and 66.7% (n=44) of the sample were female. All patients had suffered from tinnitus and this had been followed by loss of serviceable hearing on the affected side in 89.4% (n=59) of cases. Preoperative facial palsy was found in 53% (n=35) of patients. The mean tumor size was 40.35 mm. Gross-total resection (GTR) was achieved in 24 (36.36%) cases, while near-total resection (NTR) was obtained in 42 (63.64%) cases. New-onset facial palsy or degradation of the preoperative facial deficit occurred in 12 (18.18%) cases, most of whom were patients with a GTR (n=9, 37.5%). This was statistically significant. There were no significant postoperative differences between the GTR and NTR groups. There was one death in the GTR group. CONCLUSIONS: We conclude that near-total tumor removal provides good surgical results and better postsurgical quality of life for patients when compared to gross-total tumor resection. Therefore, this should be the end goal of the resection of large VSs.