Associations of miR-181a with Health-Related Quality of Life, Cognitive Functioning, and Clinical Data of Patients with Different Grade Glioma Tumors.

Gliomas are central nervous system tumors with a lethal prognosis. Small micro-RNA molecules participate in various biological processes, are tissue-specific, and, therefore, could be promising targets for cancer treatment. Thus, this study aims to examine miR-181a as a potent biomarker for the diagnosis and prognosis of glioma patients and, for the first time, to find associations between the expression level of miR-181a and patient quality of life (QoL) and cognitive functioning. The expression level of miR-181a was analyzed in 78 post-operative II-IV grade gliomas by quantitative real-time polymerase chain reaction. The expression profile was compared with patient clinical data (age, survival time after the operation, tumor grade and location, mutation status of isocitrate dehydrogenase 1 (IDH1), and promoter methylation of O-6-methylguanine methyltransferase). Furthermore, the health-related QoL was assessed using the Karnofsky performance scale and the quality of life questionnaires; while cognitive assessment was assessed by the Hopkins verbal learning test-revised, trail-making test, and phonemic fluency tasks. The expression of miR-181a was significantly lower in tumors of grade III and IV and was associated with IDH1 wild-type gliomas and a worse prognosis of patient overall survival. Additionally, a positive correlation was observed between miR-181a levels and functional status and QoL of glioma patients. Therefore, miR-181a is a unique molecule that plays an important role in gliomagenesis, and is also associated with changes in patients' quality of life.

Mesenchymal and Proneural Subtypes of Glioblastoma Disclose Branching Based on GSC Associated Signature.

Glioblastomas (GBM)-the most common, therapy-resistant, and lethal tumors driven by populations of glioma stem cells (GSCs) are still on the list of the most complicated pathologies. Thus, deeper understanding and characterization of GSCs is indispensable to find suitable targets and develop more effective therapies. In the present study, we applied native glioblastoma cells and GSCs sequencing, screened for GSC-specific targets and checked if the signature is related to GBM patient pathological, clinical data as well as molecular subtypes applying TCGA cohort. Data analysis revealed that tumors of proneural and mesenchymal subtypes are branching in separate clusters based on screened gene expression. Samples of the same subtype revealed significantly different patient survival prognosis as well as recurrence chance between the clusters. Recently, different subpopulations of mesenchymal GSC demonstrating different properties were shown, which indicates possible internal heterogeneity of GBM subtypes as well. Current findings also revealed branching of molecular GBM subtypes that were significantly linked to patient outcome and that might be decided by distinct GSC subpopulations.

The Role of CASC2 and miR-21 Interplay in Glioma Malignancy and Patient Outcome.

Recently long non-coding RNAs (lncRNAs) were highlighted for their regulatory role in tumor biology. The novel human lncRNA cancer susceptibility candidate 2 (CASC2) has been characterized as a potential tumor suppressor in several tumor types. However, the roles of CASC2 and its interplay with miR-21 in different malignancy grade patient gliomas remain unexplored. Here we screened 99 different malignancy grade astrocytomas for CASC2, and miR-21 gene expression by real-time quantitative polymerase chain reaction (RT-qPCR) in isocitrate dehydrogenase 1 (IDH1) and O-6-methylguanine methyltransferase (MGMT) assessed gliomas. CASC2 expression was significantly downregulated in glioblastomas (p = 0.0003). Gliomas with low CASC2 expression exhibited a high level of miR-21, which was highly associated with the higher glioma grade (p = 0.0001), IDH1 wild type gliomas (p < 0.0001), and poor patient survival (p < 0.001). Taken together, these observations suggest that CASC2 acts as a tumor suppressor and potentially as a competing endogenous RNA (ceRNA) for miR-21, plays important role in IDH1 wild type glioma pathogenesis and patients' outcomes.

Unique Interplay Between Molecular miR-181b/d Biomarkers and Health Related Quality of Life Score in the Predictive Glioma Models.

In the last decade, an increasing amount of research has been conducted analyzing microRNA expression changes in glioma tissue and its expressed exosomes, but there is still sparse information on microRNAs or other biomarkers and their association with patients' functional/psychological outcomes. In this study, we performed a combinational analysis measuring miR-181b and miR-181d expression levels by quantitative polymerase chain reaction (qPCR), evaluating isocitrate dehydrogenase 1 (IDH1) single nucleotide polymorphism (SNP), and O-6-methylguanine methyltransferase (MGMT) promoter methylation status in 92 post-surgical glioma samples and 64 serum exosomes, including patients' quality of life evaluation applying European Organization for Research and Treatment of Cancer (EORTC) questionnaire for cancer patients (QLQ-30), EORTC the Brain Cancer-Specific Quality of Life Questionnaire (QLQ-BN20), and the Karnofsky performance status (KPS). The tumoral expression of miR-181b was lower in grade III and glioblastoma, compared to grade II glioma patients (p < 0.05). Additionally, for the first time, we demonstrated the association between miR-181 expression levels and patients' quality of life. A positive correlation was observed between tumoral miR-181d levels and glioma patients' functional parameters (p < 0.05), whereas increased exosomal miR-181b levels indicated a worse functional outcome (p < 0.05). Moreover, elevated miR-181b exosomal expression can indicate a significantly shorter post-surgical survival time for glioblastoma multiforme (GBM) patients. In addition, both tumoral and exosomal miR-181 expression levels were related to patients' functioning and tumor-related symptoms. Our study adds to previous findings by demonstrating the unique interplay between molecular miR-181b/d biomarkers and health related quality of life (HRQOL) score as both variables remained significant in the predictive glioma models.

A SEMA3 Signaling Pathway-Based Multi-Biomarker for Prediction of Glioma Patient Survival.

Glioma is a lethal central nervous system tumor with poor patient survival prognosis. Because of the molecular heterogeneity, it is a challenge to precisely determine the type of the tumor and to choose the most effective treatment. Therefore, novel biomarkers are essential to improve the diagnosis and prognosis of glioma tumors. Class 3 semaphorin proteins (SEMA3) play an important role in tumor biology. SEMA3 transduce their signals by using neuropilin and plexin receptors, which functionally interact with the vascular endothelial growth factor-mediated signaling pathways. Therefore, the aim of this study was to explore the potential of SEMA3 signaling molecules for prognosis of glioma patient survival. The quantitative real-time PCR method was used to evaluate mRNA expression of SEMA3(A-G), neuropilins (NRP1 and NRP2), plexins (PLXNA2 and PLXND1), cadherins (CDH1 and CDH2), integrins (ITGB1, ITGB3, ITGA5, and ITGAV), VEGFA and KDR genes in 59 II-IV grade glioma tissues. Seven genes significantly associated with patient overall survival were used for multi-biomarker construction, which showed 64%, 75%, and 68% of accuracy of predicting the survival of 1-, 2-, and 3-year glioma patients, respectively. The results suggest that the seven-gene signature could serve as a novel multi-biomarker for more accurate prognosis of a glioma patient's outcome.

Isocytosine deaminase Vcz as a novel tool for the prodrug cancer therapy.

BACKGROUND: The cytosine deaminase (CD)/5-fluorocytosine (5-FC) system is among the best explored enzyme/prodrug systems in the field of the suicide gene therapy. Recently, by the screening of the environmental metagenomic libraries we identified a novel isocytosine deaminase (ICD), termed Vcz, which is able of specifically converting a prodrug 5-fluoroisocytosine (5-FIC) into toxic drug 5-fluorouracil (5-FU). The aim of this study is to test the applicability of the ICD Vcz / 5-FIC pair as a potential suicide gene therapy tool. METHODS: Vcz-expressing human glioblastoma U87 and epithelial colorectal adenocarcinoma Caco-2 cells were treated with 5-FIC, and the Vcz-mediated cytotoxicity was evaluated by performing an MTT assay. In order to examine anti-tumor effects of the Vcz/5-FIC system in vivo, murine bone marrow-derived mesenchymal stem cells (MSC) were transduced with the Vcz-coding lentivirus and co-injected with 5-FIC or control reagents into subcutaneous GL261 tumors evoked in C57/BL6 mice. RESULTS: 5-FIC alone showed no significant toxic effects on U87 and Caco-2 cells at 100 µM concentration, whereas the number of cells of both cell lines that express Vcz cytosine deaminase gene decreased by approximately 60% in the presence of 5-FIC. The cytotoxic effects on cells were also induced by media collected from Vcz-expressing cells pre-treated with 5-FIC. The co-injection of the Vcz-transduced mesenchymal stem cells and 5-FIC have been shown to augment tumor necrosis and increase longevity of tumorized mice by 50% in comparison with control group animals. CONCLUSIONS: We have confirmed that the novel ICD Vcz together with the non-toxic prodrug 5-FIC has a potential of being a new enzyme/prodrug system for suicide gene therapy.

Association of COMT Val158Met Polymorphism With Delirium Risk and Outcomes After Traumatic Brain Injury.

OBJECTIVE: The authors investigated the association of the catechol-o-methyltransferase (COMT) gene Val158Met polymorphism with delirium risk and functional and cognitive outcomes among patients with complicated mild to moderate traumatic brain injury (TBI). METHODS: In a prospective observational cohort study, patients were monitored for occurrence of delirium during the first 4 days of admission by using the Confusion Assessment Method. Functional and cognitive outcomes were evaluated with the Glasgow Outcome on Discharge Scale and the Montreal Cognitive Assessment test, respectively. Eighty-nine patients were included in the study; of these, 17 (19%) were diagnosed with delirium. RESULTS: The COMT Val158/Val158 polymorphism was associated with increased risk of delirium in multivariable regression analyses adjusted for alcohol misuse, history of neurological disorder, age, and admission Glasgow Coma Scale score (odds ratio=4.57, 95% CI=1.11, 18.9, p=0.036). The COMT Met158 allele was associated with better functional outcomes in univariate analysis (odds ratio=2.82, 95% CI=1.10, 7.27, p=0.031) but not in multivariable analysis (odds ratio=2.33, 95% CI=0.89, 6.12, p=0.085). Cognitive outcomes were not associated with the COMT Val158Met polymorphism in univariate regression analysis (p=0.390). Delirium was a significant predictor of worse functional and cognitive outcomes in multivariable regression analyses adjusted for other risk factors (odds ratio=0.04, 95% CI=0.01, 0.16, p<0.001, and ß=-3.889, 95% CI=-7.55, -0.23, p=0.038, respectively). CONCLUSIONS: The COMT genotype is important in delirium risk and functional outcomes of patients with mild to moderate TBI. Whether the COMT genotype is associated with outcomes through incident delirium remains to be determined in larger studies.

Prognostic role of high sensitivity C-reactive protein and interleukin-6 in glioma and meningioma patients.

High sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) can be important prognostic indicators of brain tumor patients. We investigated the association of circulating IL-6 and hsCRP concentrations with discharge outcomes and survival of glioma and meningioma patients. One-hundred and sixty-three (115 women; median age 57 years) patients admitted for meningioma (n = 94), high-grade glioma (n = 48) and low-grade glioma (n = 21) surgery were enrolled in this prospective cohort study. Serum samples were collected within 24 h of admission. Discharge outcome was evaluated using the Glasgow Outcome Scale (unfavorable outcome = score from 1 to 3). Follow-up continued until November, 2016. Elevated IL-6 (≥ 2 pg/ml) and hsCRP (≥ 1 mg/l) concentrations were present in 25 and 35% of brain tumor patients, respectively. Elevated IL-6 concentrations were associated with unfavorable outcome at hospital discharge, adjusting for brain tumor histological diagnosis, patient age and gender (OR 2.39, 95% CI 0.97-5.91, p = 0.05). Elevated hsCRP concentrations were not associated with discharge outcome (p = 0.13). In multivariate Cox regression analyses adjusted for patient age, gender, extent of tumor resection and adjuvant treatment, elevated IL-6 concentration was associated with greater mortality risk in high-grade glioma patients (OR 2.623; 95% CI 1.129-5.597; p = 0.01), while elevated hsCRP concentration was associated with greater mortality risk in meningioma patients (OR 3.650; 95% CI 1.038-12.831; p = 0.04). Elevated IL-6 concentration is associated with greater unfavorable outcome risk in brain tumor patients and with greater mortality in high-grade glioma patients, while elevated hsCRP concentration is associated with greater mortality in meningioma patients.

Brain MRI morphometric analysis in Parkinson's disease patients with sleep disturbances.

BACKGROUND: Sleep disturbances are common in patients with advanced Parkinson disease (PD). The aim of this study was to evaluate a possible association of cortical thickness, cortical and subcortical volume with sleep disturbances in PD patients. METHODS: Twenty-eight PD patients (14 men and 14 women, median age 58 years) were evaluated for sleep disturbances with PDSS and underwent brain MRI. Control group consisted of 28 healthy volunteers who were matched by age and gender. Automated voxel based image analysis was performed with the FreeSurfer software. RESULTS: PD patients when compared to controls had larger ventricles, smaller volumes of hippocampus and superior cerebellar peduncle, smaller grey matter thickness in the left fusiform, parahipocampal and precentral gyruses, and right caudal anterior cingulate, parahipocampal and precentral hemisphere gyruses, as well as smaller volume of left rostral middle frontal and frontal pole areas, and right entorhinal and transverse temporal areas. According to the Parkinson's disease Sleep Scale (PDSS), 15 (53.58%) patients had severely disturbed sleep. The most frequent complaints were difficulties staying asleep during the night and nocturia. The least frequent sleep disturbances were distressing hallucinations and urine incontinence due to off symptoms. Patients who fidgeted during the night had thicker white matter in the left caudal middle frontal area and lesser global left hemisphere cortical surface, especially in the lateral orbitofrontal and lateral occipital area, and right hemisphere medial orbitofrontal area. Patients with frequent distressful dreams had white matter reduction in cingulate area, and cortical surface reduction in left paracentral area, inferior frontal gyrus and right postcentral and superior frontal areas. Nocturnal hallucinations were associated with volume reduction in the basal ganglia, nucleus accumbens and putamen bilaterally. Patients with disturbing nocturia had reduction of cortical surface on the left pre- and postcentral areas, total white matter volume decrease bilaterally as well in the pons. CONCLUSIONS: PD patients with nocturnal hallucinations had prominent basal ganglia volume reduction. Distressful dreams were associated with limbic system and frontal white matter changes, meanwhile nocturia was mostly associated with global white matter reduction and surface reduction of cortical surface on the left hemisphere pre- and postcentral areas.

Incidence and clinical significance of postoperative delirium after brain tumor surgery.

BACKGROUND: Delirium is an acute and reversible deterioration of mental state. Postoperative delirium (POD) can develop after surgical procedures and is associated with impaired health status and worse recovery. So far, there is little data about postoperative delirium after brain surgery. The aim of this study was to evaluate frequency, risk factors, and prognostic value of POD in predicting short-term postoperative outcomes after brain tumor surgery. METHODS: Five-hundred and twenty-two patients who underwent elective brain tumor surgery in 2010-2017 were included in this prospective study. Patients were monitored for POD using the Confusion Assessment Method for the ICU (CAM-ICU) for 2 to 7 days after the surgery. At hospital discharge, outcomes were evaluated using the Glasgow Outcome Scale (GOS). RESULTS: POD was diagnosed in 22 (4.2%) patients. Risk factors of POD were low level of hemoglobin, poor functional status at time of admission, low education level and older age (65 years and older). POD incidence was not associated with brain tumor laterality, location, extent of resection, histological diagnosis, or affected brain lobe. POD was associated with greater risk for unfavorable outcomes at hospital discharge (OR = 5.3; 95% CI [2.1-13.4], p = 0.001). CONCLUSIONS: POD is not a common complication after elective brain tumor surgery. Older age, poor functional status, low education level and anemia are associated with greater POD risk. Extent of surgical intervention and brain tumor location are not associated with POD risk. POD is associated with worse outcome at hospital discharge.

Prothrombin Complex Concentrate for Warfarin-Associated Intracranial Bleeding in Neurosurgical Patients: A Single-Center Experience.

Objective: The number of patients presenting with warfarin-associated intracranial bleeding and needing neurosurgical intervention is growing. Prothrombin complex concentrate (PCC) is commonly used for anti-coagulation reversal before emergent surgery. We present our experience with PCC use in patients presenting with coagulopathy and needing urgent craniotomy. Methods: We retrospectively identified all patients presenting with intracranial bleeding and coagulopathy due to warfarin use, requiring urgent neurosurgical procedures, from January, 2014 (implementation of 4-PCC therapy) until December, 2016. For coagulation reversal, all patients received 4-PCC (Octaplex) and vitamin K. Results: Thirty-five consecutive patients (17 men; median age 72 years) were administered 4-PCC before emergent neurosurgical procedures. The majority of patients presented with traumatic subdural hematoma (62%) and spontaneous intracerebral hemorrhage (32%). All patients were taking warfarin. Median international normalized ratio (INR) on admission was 2.94 (range: 1.20 to 8.60). Median 4-PCC dose was 2000 I.U. (range: 500 I.U. to 3000 I.U.). There was a statically significant decrease in INR (p < 0.01), PT (p < 0.01), and PTT (p = 0.02) after 4-PCC administration. Postoperative INR values were ≤3.00 in all patients, and seven (20%) patients had normal INR values. There were no 4-PCC related complications. Four (11%) patients developed subdural/epidural hematoma and 20 (57%) patients died. Mortality was associated with lower Glasgow coma scale (GCS) score. Conclusions: The 4-PCC facilitates INR reversal and surgery in patients presenting with warfarin-associated coagulopathy and intracranial bleeding requiring urgent neurosurgical intervention.

Signal transducer and activator of transcription 3 (STAT3) promoter methylation and expression in pituitary adenoma.

BACKGROUND: Pituitary adenoma (PA) is a benign brain tumor that can cause neurological, endocrinological and ophthalmological aberrations. Till now there is a need to identify factors that can influence the tumor invasiveness and recurrence. The aim of this study was to evaluate the associations between the signal transducer and activator of transcription 3 (STAT3) promoter methylation, mRNA expression and the invasiveness or recurrence of PAs and patient clinical characteristics. METHODS: Study participants comprised of 102 subjects with a diagnosis of PA: 54 functioning and 48 non-functioning, 58 invasive and 30 non-invasive PAs and 14 relapses. The bisulfite treatment of tumor DNA and methylation-specific polymerase chain reaction (MS-PCR) method was used to determine the STAT3 gene promoter methylation. For the STAT3 mRNA expression, the first-strand cDNA was produced from total RNA by using reverse transcriptase and quantitative real-time PCR (qRT-PCR) was performed. RESULTS: In 10.78% (11/102) of PA tissues STAT3 gene promoter was methylated. A gender of male and patient group older than 60 years were significantly associated with reduced STAT3 mRNA expression (Mann-Whitney test, p = 0.025, p = 0.047, respectively). However, no more statistical differences were found between STAT3 promoter methylation, mRNA expression and patient clinical characteristics or PA invasiveness or recurrence. CONCLUSIONS: Further investigations are needed to clarify the influence of STAT3 gene promoter methylation and mRNA expression changes in PAs.

Association of thyroid hormone concentrations with quality of life of primary brain tumor patients: a pilot study.

Reduced triiodothyronine (T3) concentrations were implicated in worse prognosis of brain tumor patients. In this study we investigated the association of normal and abnormal thyroid hormone concentrations with health-related quality of life (HRQoL) of patients with primary brain tumors. Sixty-three patients (67% women and a mean age of 55.5 ± 13.8 years) before brain tumor surgery were evaluated for: (1) HRQoL using the EORTC questionnaire for cancer patients (QLQ-C30) and the Brain Cancer-Specific Quality of Life Questionnaire (QLQ-BN20); (2) functional status (Barthel Index); and (3) clinical disease severity. Blood samples were obtained for assessment of thyroid hormone concentrations before surgery. After adjusting for the brain tumor histological diagnosis, patients' age, gender and functional status, lower thyroid stimulating hormone (TSH) concentrations were associated with poor levels of functioning on the QLQ-C30 scales: physical functioning (ß = 0.395, p < 0.001), role functioning (ß = 0.334, p = 0.003) and cognitive functioning (ß = 0.327, p = 0.009), and with greater QLQ-BN20 fatigue symptom severity (ß = -0.406, p < 0.001). Lower free T3 concentrations were associated with worse HRQOL on the QLQ-C30 global health status (ß = 0.302, p = 0.017), emotional functioning (ß= 0.422, p < 0.001) and cognitive functioning (ß= 0.259, p = 0.042) domains, and with greater symptom severity on the QLQ-BN20 fatigue (ß = -0.238, p = 0.041), motor dysfunction (ß = -0.283, p = 0.013) and weakness of legs (ß = -0.269. p = 0.027) domains. In conclusion, reduced T3 and TSH hormone concentrations are associated with impaired emotional and physical aspects of HRQoL of primary brain tumor patients independent of brain tumor histological diagnosis, patients' age, gender and functional status. Assessment for thyroid axis dysfunction should be addressed and appropriately managed in neuro-oncology patient care.

The association between lunar phase and intracranial aneurysm rupture: Myth or reality? Own data and systematic review.

BACKGROUND: It is a common belief in medical community that lunar phases have an impact on human health. A growing body of evidence indicates that lunar phases can predict the risk to develop acute neurological and vascular disorders. The goal of present report was to present our institution data and to perform systematic review of studies examining the association of intracranial aneurysm rupture with moon phases. METHODS: We identified all patients admitted to our department for ruptured intracranial aneurysms in a period between November, 2011 and December, 2014. Patients with a known aneurysm rupture date were included. Lunar phases were determined by dividing lunar month (29.5 days) into eight equal parts, i.e., new moon, waxing crescent, first quarter, waxing gibbous, full moon, waning gibbous, last quarter and waning crescent. A systematic literature review was undertaken to identify studies that evaluated the association of lunar phases with the incident of intracranial aneurysm rupture. RESULT: One hundred and eighty-six patients (62 men and 124 women, median age 56 years) were admitted to our department for treatment of ruptured intracranial aneurysms. The rate of intracranial aneurysm rupture was equally distributed across all phases of the lunar cycle (X 2 [7; 185] = 12.280, p = 0.092). We identified three studies that evaluated the association between incident intracranial aneurysm rupture and lunar phases with a total of 1483 patients. One study from Lebanon found that the incidence rate of intracranial aneurysm rupture was statistically significantly greater during the new moon phase (25% cases), relative to the other seven lunar phases (p < 0.001). Two subsequent studies from Austria and Germany in larger patient samples (n = 717 and n = 655, respectively) did not find an association between lunar phases and intracranial aneurysm rupture (p-values of 0.84 and 0.97, respectively). When analyzing all four studies together, we did not find an association between lunar phases and incidence of intracranial aneurysm rupture (X 2 [1668; 7] = 2.080, p = 0.955). CONCLUSIONS: Moon phases are not associated with incidence of intracranial aneurysm rupture. Studies investigating the association of intracranial aneurysm rupture with lunar illumination defined using more sensitive approaches are encouraged.

Safety and efficacy of stereotactic aspiration with fibrinolysis for deep-seated spontaneous intracerebral hemorrhages: A single-center experience.

OBJECTIVE: The aim of this study was to evaluate feasibility and safety of stereotactic aspiration with fibrinolysis of deep-seated intracerebral hemorrhages (ICH). MATERIALS AND METHODS: From March 1995 until December 2016, 58 adult patients (34 men and 24 women; mean age of 56.8±11.8 years) presenting with deep-seated spontaneous supratentorial ICH were treated using a minimally invasive technique. Intracerebral hematomas were aspirated until obvious resistance to free-hand suction and subsequent clot fibrinolysis was done using either streptokinase or recombinant tissue-type plasminogen activator. CT scans were performed at intervals ranging from 24 to 72h. At discharge, functional outcomes were evaluated using the Glasgow outcome scale (GOS). The 30-day mortality rate was evaluated in all patients. RESULTS: The average ICH volume on initial CT scan was 34.7±11.1cm3 (range, 20-90cm3). Mean residual hematoma volume after the treatment was 8.0±5.1cm3 (range, 3-32cm3). There was statistically significant reduction of ICH volume after the treatment (P<0.001). Median ICH reduction rate was 5cm3/d (range, 1.5-16.0cm3/d) and 17.2%/d (range, 5.27-40.0%/d). Median discharge GOS score was 3 (range, 1-4). Six (10.9%) patients died during the 30-day follow-up period. Treatment related complications were observed in three (5.5%) patients. In two patients asymptomatic increase of ICH volume occurred and one patient was diagnosed with CNS infection. CONCLUSIONS: Stereotactic clot aspiration with subsequent fibrinolytic therapy is safe and feasible treatment procedure associated with significant hematoma resolution rates and acceptable patient outcomes.

Suicidal ideation in patients undergoing brain tumor surgery: prevalence and risk factors.

PURPOSE: Suicidal ideation (SI) is an important complication in cancer patients that should be promptly recognized and adequately managed. We investigated the prevalence rate and correlates of pre-operative SI in brain tumor (BT) patients admitted for elective BT surgery. METHODS: Two hundred and eleven consecutive patients (70 % women; mean age 55.9 ± 15.4 years) scheduled for BT surgery were evaluated for SI ("suicidal thought" item from the Beck Depression Inventory-II), depressive/anxiety symptom severity (Hospital Anxiety and Depression scale (HADS)), health-related quality of life (SF-36 scale), functional status (Barthel Index), and psychiatric histories and treatments. The majority of patients were diagnosed with meningioma (39 %) and high-grade glioma (17 %). RESULTS: SI was self-reported by 12 (6 %) patients. Patients expressing SI were most commonly diagnosed with meningioma (50 %). Patients with SI were more likely to have a past history of psychiatric disorders, scored higher on the HADS anxiety subscale, and reported worse health-related quality of life across physical and mental health domains. In multivariate regression analyses, worse perceived mental health was associated with increased risk for SI independently from clinical, sociodemographic, and other patient-oriented variables considered in the study. CONCLUSIONS: SI was self-reported by 6 % of BT patients before surgical intervention and was associated with a past history of psychiatric disorders and worse perceived health status. Poor mental health was an independent correlate of SI. The perception of health status by a patient should be considered as an important determinant of poor mental health in BT patients.

Olfactory Fossa Meningioma Presenting as Depressive Disorder: A Case Report.

Meningiomas are common, usually benign intracranial tumors. They grow slowly and can remain asymptomatic for many years. Meningiomas can present as mental disorders rather than with neurologic signs or symptoms. In this case report we describe a middle-aged man with a 2-year history of depressive disorder who was diagnosed with a large olfactory fossa meningioma after he developed mental status changes and urinary incontinence. After the tumor was removed, the patient's depressive symptoms resolved and his neurocognitive functions improved. We discuss the patient's neuropsychological and psychiatric profiles to identify symptoms and other clues that could expedite identification of meningiomas in patients with psychiatric disorders. Because olfactory fossa meningiomas can present as depressive disorder, we recommend brain imaging to rule out organic brain lesions in middle-aged and older patients with new-onset psychiatric symptoms. Although tumor removal brought improvement of our patient's mental state and neurocognitive functions, patients may not be able to recover their cognitive functions completely.

Professional burnout and its correlates in Lithuanian neurosurgeons.

BACKGROUND: This study aimed to evaluate prevalence and severity of professional burnout in a sample of Lithuanian neurosurgeons and to analyze its personal, interpersonal, and organizational correlates. METHOD: Thirty-one out of 79 (response rate 39 %) Lithuanian neurosurgeons participated in the study. Professional burnout was evaluated using the Maslach Burnout Inventory - General Survey. Participants also answered questions about professional stressors, sources of professional dissatisfaction, life-style factors, sickness absenteeism/presenteeism, and professional practice. RESULTS: The majority of neurosurgeons were between 41 and 60 years of age (48 %), were married (97 %), had children (84 %). Most neurosurgeons had 20 or more years of professional experience (54.9 %), worked from 41 to 60 h per week (58 %), and performed up to 150 surgeries per year (77.4 %). Eight (26 %) neurosurgeons reported a high level of emotional exhaustion, five (16 %) reported high level of cynicism, and eight (26 %) reported low professional efficacy. Correlation analyses revealed that higher number of surgeries per year, more hours devoted to clinical work, opportunities for professional development, intellectual challenges at work, appreciation by the patients and prestige of the profession were related to lower level of burnout. Greater general workload, unpredictability of the work schedule, lack of necessary technical equipment, dissatisfaction with colleagues, and uncertainty about the future were related to a higher level of burnout. CONCLUSIONS: Burnout was reported by one-quarter of neurosurgeons who chose to participate in the study. Personal, interpersonal, and organizational factors arising while fulfilling professional duties were important correlates of neurosurgeons' burnout. Due to the moderate response rate, our results should be interpreted with caution. Larger studies evaluating burnout among European neurosurgeons are needed.

Hemodynamic response during aneurysm clipping surgery among experienced neurosurgeons.

BACKGROUND: Neurosurgery is a challenging field associated with high levels of mental stress. The goal of this study was to investigate the hemodynamic response of experienced neurosurgeons during aneurysm clipping surgery and to evaluate whether neurosurgeons' hemodynamic responses are associated with patients' clinical statuses. METHODS: Four vascular neurosurgeons (all male; mean age 51 ± 10 years; post-residency experience ≥7 years) were studied during 42 aneurysm clipping procedures. Blood pressure (BP) and heart rate (HR) were assessed at rest and during seven phases of surgery: before the skin incision, after craniotomy, after dural opening, after aneurysm neck dissection, after aneurysm clipping, after dural closure and after skin closure. RESULTS: HR and BP were significantly greater during surgery relative to the rest situation (p ≤ 0.03). There was a statistically significant increase in neurosurgeons' HR (F [6, 41] = 10.88, p < 0.001), systolic BP (F [6, 41] = 2.97, p = 0.01), diastolic BP (F [6, 41] = 2.49, p = 0.02) and mean BP (F [6, 41] = 3.36, p = 0.003) during surgery. The greatest mean HR was after aneurysm clipping, and the greatest BP was after aneurysm neck dissection. Systolic, diastolic and mean BPs were significantly greater during surgical clipping for unruptured aneurysms compared to ruptured aneurysms across all stages of surgery (p ≤ 0.002); however, after adjusting for neurosurgeon experience, the difference in BP as a function of aneurysm rupture was not significant (p > 0.08). Aneurysm location, intraoperative aneurysm rupture, admission WFNS score, admission Glasgow Coma Scale scores and Fisher grade were not associated with neurosurgeons' intraoperative HR and BP (all p > 0.07). CONCLUSIONS: Aneurysm clipping surgery is associated with significant hemodynamic system activation among experienced neurosurgeons. The greatest HR and BP were after aneurysm neck dissection and clipping. Aneurysm location and patient clinical status were not associated with intraoperative changes of neurosurgeons' HR and BP.

Predictors of health-related quality of life in neurosurgical brain tumor patients: focus on patient-centered perspective.

BACKGROUND: In brain tumor (BT) patients, the association between health-related quality of life (HRQoL) and psychological characteristics remains largely unknown. We evaluated the association of personality traits, clinical factors, psychological distress symptoms, and cognitive state with HRQoL in BT patients. METHODS: On admission for BT surgery, 200 patients (69 % women; age 55.8 ± 14.5 years) were evaluated for HRQoL (SF-36 scale), Big-Five personality traits (Ten-Item Personality Inventory), psychological distress symptoms (Hospital Anxiety and Depression Scale or HADS), cognitive function (Mini-Mental State Examination or MMSE) and clinical characteristics, including functional status (Barthel index or BI). The most common BT diagnoses were meningioma (39 %) and high-grade glioma (18 %). RESULTS: Only factors significantly associated with SF-36 domains in univariable regression analyses were included in their respective multivariable models and predicted from 6 %-49 % of the total variance of SF-36 scores. Greater TIPI emotional stability score was independently associated with greater SF-36 emotional well-being (ß = 0.23, p < 0.001) and general health (ß = 0.18, p = 0.01) scores, and greater TIPI consciousness score, with greater SF-36 emotional well-being score (ß = 0.13, p = 0.02). HADS-anxiety and HADS-depression scores were the strongest independent determinants of all, except physical functioning, SF-36 scores (ß-values range from 0.14 to 0.56; p values ≤ 0.03). BI score was the strongest independent determinant of SF-36 physical functioning score (ß = 0.36, p < 0.001). MMSE score was associated with all but emotional well-being and social functioning SF-36 scores. CONCLUSIONS: Consciousness and emotional stability should be considered important personality-related determinants of HRQoL in BT patients. Psychological distress, functional disability, and cognitive impairment are also important predictors of HRQoL.