Quantitative profiling of genes associated with cancer pathways in brain tumors.

BACKGROUND: Brain tumors are a heterogeneous group of malignancies characterized by inter- and intratumoral heterogeneity. Among them, the most aggressive and, despite advances in medicine, still incurable remains glioblastoma. One of the reasons is the high recurrence rate of the disease and resistance to temozolomide, a golden standard in chemotherapy of brain tumors. Therefore, mapping the pathways responsible for tumorigenesis at the transcriptional level may help to determine the causes and aggressive behavior among different glial tumors. PATIENTS AND METHODS: Biopsies from patients with astrocytoma (N = 6), glioblastoma (N = 22), and meningioma (N = 14) were included in the sample set. A control group consisted of RNA isolated from healthy human brain (N = 3). The reverse-transcribed cDNAs were analyzed using the Human Cancer PathwayFinder™ real-time PCR Array in a 96-well format. The expression of 84 genes belonging to 9 signaling pathways (angiogenesis, apoptosis, cell cycle and senescence, DNA damage and repair, epithelial-to-mesenchymal transition, hypoxia, overall metabolism, and telomere dynamics) was determined for each sample. RESULTS: By determining the relative expression of selected genes, we characterized the transcriptomic profile of individual brain malignancies in the context of signaling pathways involved in tumorigenesis. We observed deregulation in 50, 52.4 and 53.6% % of the genes in glioblastomas, meningiomas and astrocytomas, respectively. The most pronounced changes with statistical significance compared to control were observed in the genes associated with epithelial-to-mesenchymal transition (CDH2, FOXC2, GSC, SNAI2, and SOX10), cellular senescence (BMI1, ETS2, MAP2K1, and SOD1), DNA repair (DDB2, ERCC3, GADD45G, and LIG4), and dynamic of telomeres (TEP1, TERF2IP, TNKS, and TNKS2). CONCLUSION: Based on the obtained data, we can conclude that individual diagnoses differ in transcriptomic profile. An individual molecular approach is therefore necessary in order to provide comprehensive and targeted therapy on multiple metabolic pathways in the diagnosis of brain tumors.

Is obesity a significant risk factor of symptomatic spinal epidural hematoma after elective degenerative lumbar spine surgery?

INTRODUCTION: The occurrence of symptomatic spinal epidural hematoma after spine surgery is a rare, but serious major complication whose incidence usually requires urgent surgical intervention. Obesity is currently considered to be one of the most common metabolic diseases. METHODS: Prospective analysis of patients who underwent surgical treatment of degenerative lumbar spine disease from January 2016 to February 2018 with one-year follow-up. All patients underwent decompression of spinal cord and nerve roots. This study was conducted to determine an association between the incidence of spinal epidural hematoma (SEDH) requiring surgical treatment and obesity/body mass index (BMI). RESULTS: In our study, data from 371 patients were assessed. SEDH requiring surgical intervention occurred totally in seven patients (1.89 %). An average BMI in patients with presence of SEDH was 30.67 kg/m2. Our work showed a statistically significant difference between BMI in patients with SEDH compared to patients without SEDH (p = 0.0044). This study also showed a significant difference in incidence of symptomatic SEDH in obese patients compared to non-obese patients (p=0.0158). CONCLUSION: In our study, we found out that obesity is a significant risk factor for the incidence of postoperative SEDH after degenerative lumbar spine surgery (Tab. 1, Fig. 2, Ref. 18).

Analysis of clinical efficiency and early postoperative complications after cranioplasty.

INTRODUCTION: Despite of being considered a routine procedure, cranioplasty is associated with a substantial risk of failure, or postoperative complications. PATIENTS AND METHODS: Postoperative clinical course and rate of complications was assessed in patients undergoing cranioplasty during years 2015-2019 in a retrospective fashion. RESULTS: The most frequent condition requiring cranioplasty was a presence of bone defect after a decompressive craniectomy for traumatic brain injury (45 patients). Revision was needed in 9 cases (12.68 %), removal of the bone flap was necessary in 5 patients (7.04 %). The most common complication observed was an unintended intraoperative durotomy, occurring in 9 patients (12.68 %), which was, however, not associated with an increased risk of reoperation. Postoperative improvement of motor functions was observed in 7 patients (9.86 %). Improvement of consciousness occurred in 8 patients (11.27 %). Early cranioplasty was associated with significantly higher odds for surgical revision, patients after previous craniectomy for traumatic brain injury had significantly increased odds for the overall occurrence of complications. CONCLUSIONS: After a cranial reconstruction, complications with a various degree of severity may occur and even the result in need of the implant removal. Postoperative improvement of focal neuro-deficit is possible as well as improvement on the level of patient's consciousness (Tab. 2, Fig. 2, Ref. 61).

Noninvasive study of brain tumours metabolism using phosphorus-31 magnetic resonance spectroscopy.

Phosphorus-31 magnetic resonance spectroscopy (31P MRS) is currently not accepted as a diagnostic tool in the neuro-oncological practice, although it provides useful non-invasive information about biochemical processes ongoing in the intracranial tumours. This pilot study was aimed to present the diagnostic capability of the 31P MRS in brain tumour examination, even its application on clinical 1.5T MR scanner.Seven patients with brain tumorous lesions (four glioblastomas, one ependymoma, and two lung metastasis) underwent multivoxel in vivo 31P MRS performed on clinical 1.5 T MR scanner within measurement time of 20 minutes. Comparing two selected voxels, one in the tumour and the other one in the normal-appearing brain tissue, enabled to investigate their metabolic differences. Enhanced markers of membrane phospholipids synthesis (significantly increased phosphomonoesters ratios) than markers of their degradation (significantly decreased phosphodiesters ratios) manifested a higher cell proliferation ongoing in tumours. High energetic tumorous tissue demands leading to anaerobic metabolic turnover were present as a significant decline in phosphocreatine ratios and adenosine triphosphates. Intracellular pH evaluation showed a tumorous tendency to alkalize. 31P MRS enables the non-invasive metabolic characterization of intracranial tumours and thus appears to be a clinically useful method for the determination of ongoing tumour pathomechanisms (Fig. 2, Ref. 26). Keywords: brain tumour, 31P MRS, 1.5 Tesla; energetic metabolism.

Quantitative analysis of 2-hydroxyglutarate as a controversial oncometabolite in malignant gliomas.

There is a great effort to connect the accumulation of 2-hydroxyglutarate (2-HG) oncometabolite with cellular onco-epigenetic status and subsequently predict the prognoses of glioma patients. In this observational study, the concentrations of D- and L- 2-HG were determined in 57 tumor tissue samples of glioma patients (n=57) WHO grade I through IV (astrocytoma, oligodendroglioma, secondary glioblastoma, and glioblastoma multiforme) in vitro. Also, genetic mutation status on isocitrate dehydrogenase 1 and 2 (IDH 1/2) was determined from these samples. The objective of this study was to confirm or to reject the hypothesis of the direct correlation of 2-HG concentration in tumor tissue and the results from IDH 1/IDH 2 point mutation analyses. The concentrations of 2-HG were quantified using high sensitive HPLC and Q-TOF HRMS spectrometer setup. Concurrently, the genetic mutation analyses of both IDH 1 (cytosolic) and IDH 2 (mitochondrial) were performed by the isolation of tumor tissue DNA, PCR amplification, and subsequent Sanger forward sequencing. Our results indicate that there is no definite correlation between the two as we identified cases of glioma tumors with significantly increased concentration of one or both L- and D- 2-HG but no IDH 1/2 mutations (44% 2-HG positive cases).

Unintended durotomy during degenerative lumbar spine surgery in patients aged 60 years and older - incidence and risk factors.

ntroduction: Unintended perioperative dural tear is a common complication in spine surgery. Methods: Retrospective analysis of patients over 60 years of age who underwent surgery for degenerative disease of the lumbar spine at the Department of Neurosurgery (University Hospital in Martin) from January 2016 to December 2017. Incidence of incidental perioperative durotomy was analyzed. We analyzed selected risk factors gender, ASA (American Society of Anesthesiologists), surgical diagnosis, type of surgical performance, range of surgical procedure, revision surgery and comorbidities. The results were statistically evaluated using descriptive statistics and Fisher›s test. Results with p.

A review of possible complications in patients after decompressive craniectomy.

Through the decades of its use in the management of neurosurgical emergencies decompressive craniectomy has found its place as a life-saving procedure capable of a radical reduction of the intracranial pressure. Clinical results and rate of survival after decompressive craniectomy vary according to the primary diagnosis, and they have been a subject of multicentric randomized trials. However,  considerable attention also needs to be kept on complications associated with the craniectomy. They are based not only on the procedures invasivity but also on the pathophysiological changes associated with a conversion of the closed intracranial space to an open one. The complications may further disturb the postoperative care and convalescence in the surviving patients, and therefore in the salvageable patients the indication of decompressive craniectomy should be based on information about the expected outcome and complications rate, at the same moment prevention, early recognition and adequate therapy of the complications should be emphasized. This work describes the most common complications occurring in patients after decompressive craniectomy, their pathophysiological principles and means of treatment and prevention.

Is there an impact of subdural drainage duration and the number of burr holes on the recurrence rate of unilateral chronic subdural haematoma?

INTRODUCTION: Purpose of the study is to evaluate a possible influence of subdural drainage duration and burr hole quantity on a relapse of a unilateral chronic subdural haematoma (CHSH). METHODS: Sixty - five patients who underwent evacuation of unilateral CHSH via 1 or 2 burr holes and subdural drainage during a period from January 2014 to December 2018 were retrospectively analyzed. Duration of the subdural drainage and the number of burr holes used were assessed in relation to an incidence of CHSH recurrence. According to the subdural drainage duration, we divided the patient cohort into two subgroups: with the subdural drainage duration of 1-3 days and 4-5 days. We also evaluated a possible influence of the subdural drainage duration on risk of postoperative infection. RESULTS: An overall incidence of CHSH recurrence was 18.5%. In 45 patients treated by means of a single burr hole the haematoma recurrence was observed in 10 patients (22.2%), in 22 patients with two burr holes recurrence occurred in 2 of them (9.1%). The difference was however, not statistically significant (p=0.3214). We did not observe any significant influence of age, gender and subdural drainage duration on the incidence of CHSH recurrence. The duration of subdural drainage had not significant impact on postoperative infection rate (p=0.0950). CONCLUSION: The number of burr holes used does not affect the rate of unilateral CHSH recurrence. Similarly the duration of subdural drainage affects neither the unilateral CHSH recurrence rate nor the incidence of postoperative infection.

Subsidence of anchored cage after anterior cervical discectomy.

PURPOSE: Cage subsidence (CS) represents a risk factor for adjacent segment degeneration (ASD) and unfavorable results of anterior cervical discectomy (ACD). METHODS: Sixty-one patients after level 1 or 2 of ACD with implantation of Zero Profile VA cage were included in the study. CS was assessed with a follow-up period of 12 months after ACD. The impacts of factors such as sex, age, number of operated segments, osteoporosis and extent of peroperative distraction were assessed in relation to the incidence of CS. The influences of CS on clinical results (VAS, NDI, Odom's criteria) and ASD incidence were evaluated. RESULTS: In 74 % of cases there was the presence of CS into both adjacent vertebral bodies. CS into the ventral part of motion segment was dominant during the entire follow-up period. CS had no influence on clinical results of ACD. Parallel CS into both ventral and dorsal parts of motion segments significantly increased the incidence of proximal ASD (p = 0.0163). Osteoporosis and extent of peroperative distraction were linked to higher incidence of CS into the dorsal part of motion segment (p ˂ 0.05). CONCLUSIONS: Osteoporosis and the extent of peroperative distraction are risk factors for the subsidence of anchored cage and while increasing the incidence of proximal adjacent segment degeneration it has no significant influence on clinical results of surgery (Tab. 3, Fig. 5, Ref. 32).

Dysphagia after anterior cervical discectomy and interbody fusion - prospective study with 1-year follow-up.

INTRODUCTION: Dysphagia is a common finding after anterior cervical discectomy. The incidence and severity of swallowing disorders are variable and depend on many factors. METHODS: 73 patients after 1- or 2-level anterior cervical discectomy and fusion /ACDF/ were enrolled in prospective, single-center study. The severity of dysphagia was evaluated by the Bazaz-Yoo dysphagia score before surgery and 6 weeks, 3, 6 and 12 months after surgery. The impact of factors such as sex, age, number of operated segments, smoking, gastroesophageal reflux disease, hypertension, duration of surgery and pre-existing dysphagia on the incidence of dysphagia after surgery was verified. The correlation between the duration of surgery and severity of postoperative dysphagia, and similarly between the age and severity of preoperative and postoperative dysphagia was studied. RESULTS: Dysphagia was present in 22% patients within 12 months after surgery. No patient reported severe dysphagia. No significant relationship was demonstrated between sex, age, number of operated segments, pre-existing dysphagia, gastroesophageal reflux disease, hypertension and the incidence of dysphagia after surgery. Smokers showed a significantly lower incidence of dysphagia before surgery and within 12 months after ACDF (p.

Surgical site infections after degenerative lumbar spine surgery.

Degenerative lumbar spine disease is nowadays considered as a serious health condition, because the number of patients requiring a surgical intervention is in last decades rapidly increasing. At the time of surgery indication, it is important to assess the risk of complications incidence, especially surgical ones, because when they occur, they usually lead to reoperation, prolonged hospitalisation and drug use, economic consequences and a compromised postoperative outcome and benefits. Postoperative infectious complications may occur, even after following aseptic and hygienic epidemiological rules. This article contains an interdisciplinary review of diagnosis, treatment and prevention of postoperative surgical site infections after degenerative lumbar spine surgery. Key words: postoperative complications lumbar spine surgical treatmens - spondylodiscitis.

Heart rate variability in newborns.

Heart rate (HR) and heart rate variability (HRV) in newborns is influenced by genetic determinants, gestational and postnatal age, and other variables. Premature infants have a reduced HRV. In neonatal HRV evaluated by spectral analysis, a dominant activity can be found in low frequency (LF) band (combined parasympathetic and sympathetic component). During the first postnatal days the activity in the high frequency (HF) band (parasympathetic component) rises, together with an increase in LF band and total HRV. Hypotrophy in newborn can cause less mature autonomic cardiac control with a higher contribution of sympathetic activity to HRV as demonstrated by sequence plot analysis. During quiet sleep (QS) in newborns HF oscillations increase - a phenomenon less expressed or missing in premature infants. In active sleep (AS), HRV is enhanced in contrast to reduced activity in HF band due to the rise of spectral activity in LF band. Comparison of the HR and HRV in newborns born by physiological vaginal delivery, without (VD) and with epidural anesthesia (EDA) and via sectio cesarea (SC) showed no significant differences in HR and in HRV time domain parameters. Analysis in the frequency domain revealed, that the lowest sympathetic activity in chronotropic cardiac chronotropic regulation is in the VD group. Different neonatal pathological states can be associated with a reduction of HRV and an improvement in the health conditions is followed by changes in HRV what can be use as a possible prognostic marker. Examination of heart rate variability in neonatology can provide information on the maturity of the cardiac chronotropic regulation in early postnatal life, on postnatal adaptation and in pathological conditions about the potential dysregulation of cardiac function in newborns, especially in preterm infants.

Adverse effects of orthodontic treatments.

Orthodontic therapy, like any other medical intervention, in addition to its benefits carries the risk of potential complications and is associated with adverse effects-including periodontal problems, external root resorptions, pulpal changes, enamel damages (demineralization, discoloration, attrition), temporomandibular disorders, infective endocarditis, soft tissue damages, discomfort, pain and the risk of either aspiration or indigestion of medical instruments and appliances. Usually these effects are multifactorial in origin- most often a result of interactions between the patient, the dental practitioner and the technical aspects of the appliances or techniques. With preventive measurements and care, most of these complications can be either limited or completely avoided. Therefore, every dental practitioner must be fully aware of these effects and associated risk factors in order to maximize the treatment outcome. The present review aims to summarize these effects of orthodontic therapies, and provide a detailed description of factors and preventive measures, in order to minimize these damages.

[Urinary incontinence in degenerative spinal disease]. / Kontinencné poruchy pri degeneratívnych ochoreniach chrbtice.

PURPOSE OF THE STUDY: The aim of the study was to evaluate the presence of urinary incontinence in patients with chronic degenerative spinal disease and to identify factors affecting the occurrence and changes in urinary incontinence after surgery. MATERIAL: The group evaluated comprised 214 patients undergoing surgery for degenerative spinal disease at our department between January 1 and December 31, 2008. The patients were categorised according to the type of their degenerative disease (cervical disc herniation, lumbar disc herniation, spinal stenosis, spinal instability or olisthesis) and the spine level involved (cervical or lumbar spine). The symptoms of urinary incontinence included leakage of urine and non-obstructive chronic urinary retention developing in association with the manifestation of vertebrogenic disorder. Patients with diseases known to increase the risk of incontinence were not included in the study. METHODS: Based on a retrospective analysis of the patients' clinical notes, the occurrence of urinary incontinence in each type of degenerative spinal disease was assessed. The effect of gender, age, body mass index (BMI), neurological status and spinal disease type on the development of incontinence was statistically evaluated. The efficacy of surgical treatment was assessed on the basis of the patients' subjective complaints at the first follow-up one month after surgery. The data were evaluated by the statistical programme InSTAT (analysis of variance ANOVA, t-test). All tests were two-sided; a 0.05 level of statistical significance was used. RESULTS: Of the 214 patients with degenerative spinal disease, 27 (12.6%) had urinary incontinence. A higher risk of developing incontinence was found in women (p = 0.008) and in patients with radicular weakness (p = 0.023). The patients with urinary incontinence had their BMI significantly lower than patients without this disorder (p = 0.019). Age had no effect. The differences in the occurrence of urinary incontinence amongst the different types of degenerative disease were regarded as approaching statistical significance (p = 0.09). The surgical treatment resulted in incontinence control in 15 (55.5 %) affected patients. DISCUSSION: A comparison of the factors leading to the development of urinary incontinence in degenerative spinal disease and those associated with the development of incontinence in the general population suggests that the aetiology in each case is different. The relationship between low back pain and urinary incontinence remains unknown. CONCLUSIONS: Degenerative spinal disease can result in acute or chronic urinary incontinence. Factors associated with its development include gender, BMI, radicular weakness and the type of degenerative disease. Surgical treatment improved or eliminated the symptoms of urinary incontinence in more than half of the patients affected.