Investigation of serum E-Cadherin, VEGF121, Survivin, Tenascin C and Tetraspanin 8 levels in patients with glioblastoma.

OBJECTIVE: The aim of this study is to determine biomarkers, which may be used in order to understand the pathophysiology, the diagnosis, progression surveillance/monitoring, and treatment efficacy of high graded glial tumors. BACKGROUND: Radiological imaging in the diagnosis and relapse surveillance of glial tumors is sometimes insufficient. There is need for additional methods of diagnosis and surveillance in order to rule out contradictory circumstances. METHOD: Using enzyme like immune sorbent assay method, E-Cadherin, Tenascin C, Tetraspanin 8, Survivin and VEGF121 levels were investigated in serum and tumor tissues of 28 patients diagnosed with pathological glioblastoma, and in the serum of 26 healthy individuals. Correlation between tumor tissue values and Ki67 percentage, and P53 mutation, and difference between unhealthy and healthy serum levels were sought. RESULTS: It was found out that E-Cadherin and VEGF 121 levels in the unhealthy serum were high in comparison to the control group (p 0.05). CONCLUSION: EC and VEGF121 are biomarkers, which have the potential to be used in the diagnosis, recurrence and treatment follow-up in high graded glial tumors (Tab. 2, Fig. 1, Ref. 37). Text in PDF www.elis.sk Keywords: E-Cadherin, VEGF, Survivin, Tenascin-C, Tetraspanin, glioblastoma.

Pain and neurogenic claudication control in lumbar stenosis, which is the most common cause of spinal surgery in the geriatric population.

OBJECTIVES: The authors aim to present when to do physical therapy or surgery in geriatric patients with degenerative lumbar stenosis. METHODS: The authors retrospectively analyzed 250 patients who underwent physical therapy due to lumbar degenerative stenosis between December 2014 and April 2017. The patients were divided into two groups: Central canal stenosis and lateral recess/foraminal stenosis groups. Visual analogue scale and neurological claudication values of both patient groups were evaluated before and after physical therapy. The association between comorbid diseases and the frequency of surgery was also evaluated. RESULTS: 142 of the patients were female and 108 were male, and the mean age of these patients was 69 years. The mean onset of symptoms was 55 months. In the visual analog scale value of patients after physical therapy, the authors observed decreases of 4-6° in patients with central canal stenosis and 2-3° in patients with lateral recess/foraminal stenosis. In addition, the authors observed that patients with lateral recess/foraminal stenosis together with diabetes mellitus benefit less from physical therapy. CONCLUSION: Physical therapy and rehabilitation play an important role in the treatment of lumbar stenosis. Physical therapy is the primary treatment option for patients who do not have motor muscle strength losses and incontinence and who have pain control through medications. The authors can consider surgical interventions in patients with lateral recess/foraminal stenosis who do not benefit from physical therapy at a satisfactory level.

The effects of rivaroxaban, an oral anticoagulant, on human IVD primary cultures.

Introduction: The present study aimed to investigate the potential effects of rivaroxaban, an oral anticoagulant that inhibits the effects of factor Xa, on intact intervertebral disc tissue cells and the extracellular matrix (ECM). Material and methods: Rivaroxaban was applied to primary human cell cultures prepared from tissues of the intervertebral disc. Comparative molecular analyses were performed on non-drug-treated control group samples. Descriptive statistics were presented as the mean ± standard deviation. An analysis of variance test was performed to determine whether there were significant differences in the mean across the groups. When differences across groups were observed, Tukey's honestly significant difference post-hoc test was used for multiple pairwise comparisons. The significance of the obtained data was determined statistically. The α significance value was < 0.05. Results: The cells in the control group and in the rivaroxaban-treated group were viable, healthy, and proliferated (p < 0.05). However, the expression levels of the chondroadherin gene (CHAD), cartilage oligo matrix protein (COMP), matrix metalloproteinase (MMP)-13, and MMP-19 genes were changed (p < 0.05). Conclusions: Although rivaroxaban does not suppress cell proliferation due to morphological, biological, and biochemical changes in the intervertebral disc tissue, it may change the expression of genes that are related to ECM maintenance.

The Impact of Various Breast Sizes of Women on Vertebral Column and Spinopelvic Parameters.

AIM: To find out the anatomical changes in spine and pelvis, and the impact of various breast sizes of women on the quality of life. MATERIAL AND METHODS: Sixty women with back pain volunteered to participate in this study. Their body mass index (BMI) was calculated. Clinical evaluation of the pain was assessed using the Oswestry Disability Index and visual analogue scale. Breast volumes were measured using the Grossman Rounder device. Scoliosis radiograms were obtained, and the cervical lordosis, thoracic kyphosis, lumbar lordosis, sacral slope, pelvic incidence and pelvic tilt angles were measured in patients. The relationship between the increasing breast size and BMI was investigated through all these parameters. RESULTS: Increase in breast size positively changes the sagittal balance (r=0.356, p=0.005) and increases cervical lordosis (r=0.300, p=0.020). Increase in BMI leads to a positive sagittal balance (r=0.329, p=0.010) and increases the pelvic tilt (r=0.460, p=0.000). In patients with a positive sagittal balance, the sacral slope (r=-0.350, p=0.006) and the lumbar lordosis angle decrease (r=-0.552, p=0.000), whereas the pelvic tilt increases (r=0.298, p=0.021). CONCLUSION: Macromastia has an impact on cervical lordosis and sagittal balance, while indirectly impacting the pelvic tilt rather than the thoracic kyphosis and lumbar lordosis.

Effect of Antithrombotic Therapy on Development of Acute Subdural Hematoma After Burr Hole Drainage of Chronic Subdural Hematoma.

AIM: To evaluate the relationship between the time from cessation of anticoagulant/antiplatelet medication to surgery and risk of postoperative acute subdural hematoma (ASDH) after burr hole drainage of chronic subdural hematoma (CSDH). MATERIAL AND METHODS: A retrospective study of patients who underwent burr hole drainage of CSDH between December 2014 and December 2019 was performed. Demographic and clinical data regarding age, gender, medication (antithrombotic therapy), smoking, daily alcohol consumption, history of head trauma, presenting symptoms, and neurological examination were collected from the medical records. Patients were divided into 3 groups based on time from referral to surgery: < 24 hours, 24?72 hours, and > 72 hours. RESULTS: One hundred seventeen patients underwent burr hole drainage of CSDH during the 5-year study period. Seventy-two patients were male (61.5%) and 45 were female (38.5%). Mean age was 70.5 ± 7.2 years. Postoperative ASDH occurred in 2 of the 32 patients (6.3%) who were not taking antithrombotic medication and 6 of the 85 patients (7.1%) who were taking antithrombotic medication. The difference was not significant (p=0.797). CONCLUSION: The risk of ASDH after burr hole drainage of CSDH was not affected by antithrombotic medication. Although the literature suggests that antiplatelet and anticoagulant drugs to be discontinued between 5 and 7 days before surgery, our results showed that acute hemorrhage was not detected in any patient who underwent surgery more than 72 hours after referral.

Systematic Evaluation of Desmopressin Administered to Patients with Aneurysmal Subarachnoid Hemorrhage in the Light of the Literature.

AIM: To discuss the management of patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) developing after subarachnoid hemorrhage, in a comparative manner in the light of the literature. MATERIAL AND METHODS: Without country or language restrictions, articles with high evidential value found in electronic databases were compared to our patients? RESULTS: After the literature review, three articles were included for systematic evaluation. Desmopressin was administered to the patients for the treatment of hyponatremia, volume contraction, and negative sodium balance caused by SIADH. However, it was not used for preventing re-bleeding. CONCLUSION: To prevent the development of this complication (SIADH), the use of desmopressin, an analogue of vasopressin, is important in routine clinical practice.

Effects of etanercept, a tumor necrosis factor receptor fusion protein, on primary cell cultures prepared from intact human intervertebral disc tissue.

The aim of the present study was to investigate the effects of etanercept (ETA), a tumor necrosis factor (TNF) inhibitor, on human cell cultures prepared from intact intervertebral disc tissue. ETA is used as a treatment for cases of rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis and ankylosing spondylitis accompanied by moderate or severe joint pain. ETA was applied to primary cell cultures [annulus fibrosus and nucleus pulposus (NP) from intact intervertebral disc tissue]. Cell cultures without ETA treatment served as the control group. Morphological and quantitative molecular analyses of the two groups were performed. The number of viable cells and cell proliferation decreased in the ETA-treated cultures as compared with those in the control group. Furthermore, in the treatment group, the chondroadherin gene, an NP-specific marker, was not expressed after 24 h. By contrast, the cartilage oligo matrix protein was expressed 24, 48 and 72 h post-ETA treatment, while its expression was significantly lower than that in the control group. In addition, the expression of interleukin-1ß, as well as matrix metallopeptidase-7 and -19, was markedly decreased. Overall, the cell proliferation and gene expression in the ETA-treated cells were significantly different from those in the control group (P<0.05). These results suggest that the treatment duration and dosage of TNF inhibitors, which are used to suppress active inflammation, should be considered in the clinical setting. These biological agents may delay the healing of intervertebral disc tissue damage by slowing cell proliferation and altering gene expression via anabolic and catabolic pathways.

Investigation of the effect of dipyrone on cells isolated from intervertebral disc tissue.

The present study aimed to evaluate the effects of dipyrone, an indispensable analgesic, anti-pyretic and anti-spasmodic used in emergency departments, on nucleus pulposus and annulus fibrosus cells in vitro. After surgical biopsy, primary cell cultures were prepared from intact intervertebral disc tissues. Dipyrone was administered to the cultures in the experimental groups except for the control group. The data obtained were statistically evaluated. The proliferation was identified to be suppressed via MTT analysis. The gene expression profile of the intervertebral disc cells in the dipyrone-treated groups was significantly changed. The expression of chondroadherin, cartilage oligo matrix protein, interleukin-1ß and metalloproteinase (MMP)-19 genes were decreased, but MMP-13 and MMP-7 genes expressions were increased, as determined via reverse transcription-quantitative PCR. AO/PI staining revealed that no apoptotic or other type of cell death was detectable after administration of dipyrone does not mean that the drug is innocuous. The occurrence of cellular senescence and/or the halt of cell proliferation may also be important mechanisms underlying the adverse inhibitory effects of dipyrone. Therefore, prior to administering dipyrone in clinical practice, all possible adverse effects of this drug should be considered.

Are Intervertebral Disc Tissue Cells Damaged When Attempting to Prevent Thrombus Formation Using Dabigatran, A New Oral Anticoagulant?

AIM: To investigate the effect of dabigatran, a new oral anticoagulant, on human primary cell cultures isolated from intact intervertebral disc tissue. MATERIAL AND METHODS: Cell cultures were prepared from tissues obtained from six cases who had undergone surgery due to spinal trauma. Dabigatran, an active pharmacological agent, was applied to intact annulus fibrosus (AF)/nucleus pulposus (NP) primary cell cultures from the study group. After performing cell viability, toxicity, and proliferation tests on all cultures in the control and study groups, the surface morphologies of the samples were evaluated. Subsequently, chondroadherin (CHAD), cartilage oligomeric matrix protein (COMP), and matrix metalloproteinase (MMP)-13 and -19 expressions were measured via a real-time polymerase chain reaction (RT-PCR). Data were analyzed statistically. RESULTS: In the proliferation assays performed on the 20th day of the study, cells in the dabigatran-supplemented group were reported to have lost 46.37% more viability than those in the control group. Expressions of all genes examined except MMP-13 were evaluated in the control group by time, but in contrast to the control group results, COMP and MMP-19 gene expressions decreased in the dabigatran-treated group. No CHAD or MMP-13 expression was noted in these cultures. CONCLUSION: The potential for a systemically applied drug to accumulate in tissue and negatively affect surrounding tissues and microstructures must be emphasized.

Evaluation of the Effect of Daptomycin, a Glycopeptide Agent, on Intact Intervertebral Disc Tissue.

AIM: To evaluate the effects of pre- and intra-operatively administered daptomycin (DAP) on the intact human primary intervertebral disc tissue cells. MATERIAL AND METHODS: Primary cell cultures were established using tissues obtained through decompressive laminectomy, traumatic intervertebral disc herniation excision, and posterior transpedicular stabilization. Non-drug-administered samples were used as a control group. The samples treated with DAP formed the study group. Molecular assays for proliferation and gene expression were performed. The obtained data were evaluated statistically, and results with a value of p < 0.05 were accepted as significant. RESULTS: While no reduction was observed in the proliferation, the gene expression of intact intervertebral disc tissue cells was time-dependently decreased compared to the control group, and these results were reported to be statistically significant. CONCLUSION: This study observed the effect that a pharmaceutical preparation, which was used on intervertebral disc tissue before and after the operation, had on normal, healthy, and intact tissue. It concludes that alterations in the expression of genes involved in the anabolic and/or catabolic process, even in adjacent healthy tissue, may slow down the healing process of the damaged tissue or cause undesired cell differentiation.

Systematic Evaluation of Promising Clinical Trials-Gene Silencing for the Treatment of Glioblastoma.

AIM: To systematically investigate the role of artificial small interfering RNA (siRNA) molecules in glioblastoma treatment and to give a detailed overview of the literature concerning studies performed in this field worldwide in the last 31 years. MATERIAL AND METHODS: Articles about clinical trials conducted between December 1, 1949 and November 8, 2017, were identified from the Cochrane Collaboration, the Cochrane Library, Ovid MEDLINE, ProQuest, the National Library of Medicine, and PubMed electronic databases, using the terms "post transcriptional gene silencing," "small interfering RNA," "siRNA," and â€Å“glioblastoma," either individually or combined ("OR" and "AND"), without language and country restrictions. Articles that met the examination criteria were included in the study. After descriptive statistical evaluation, the results were reported in frequency (%). RESULTS: After scanning 2.752 articles, five articles were found that met the research criteria. Examination of full texts of the five identified articles provided no sufficient evidence for research conducted with regard to the use of gene silencing via siRNAs in glioblastoma treatment. CONCLUSION: To be able to evaluate the clinical use of siRNAs, there is an urgent need for in vivo studies and for trials with randomized, controlled, and clinical designs that provide long-term functional outcomes.

Are radio-contrast agents commonly used in discography toxic to the intact intervertebral disc tissue cells?

In the literature, there have been no studies showing clear results on how radio-contrast pharmaceuticals would affect intact disc tissue cells. In this context, it was aimed to evaluate the effects of iopromide and gadoxetic acid, frequently used in the discography, on intact lumbar disc tissue in pharmaco-molecular and histopathological level. Primary cell cultures were prepared from the healthy disc tissue of the patients operated in the neurosurgery clinic. Except for the control group, the cultures were incubated with the indicated radio-contrast agents. Cell viability, toxicity and proliferation indices were tested at specific time intervals. The cell viability was quantitatively analysed. It was also visually rechecked under a fluorescence microscope with acridine orange/propidium iodide staining. Simultaneously, cell surface morphology was analysed with an inverted light microscope, while haematoxylin and eosin (H&E) staining methodology was used in the histopathological evaluations. The obtained data were evaluated statistically. Unlike the literature, iopromide or gadoxetic acid did not have any adverse effects on the cell viability, proliferation and toxicity (P < 0.05). Although this study reveals that radio-contrast pharmaceuticals used in the discography, often used in neurosurgical practice, can be safely used, it should be remembered that this study was performed in an in vitro environment.

Effect of naproxen on proliferation and differentiation of primary cell cultures isolated from human cartilage tissue.

Non-steroidal anti-inflammatory drugs (NSAIDs) that are applied through oral, injectable or topical routes have been widely used in painful and inflammatory musculoskeletal diseases. The current study aimed to determine whether naproxen, an aryl acetic acid derivative with analgesic and anti-inflammatory effects, has a toxic effect on human chondrocytes. Samples containing monolayer primary chondrocyte cultures were prepared following resection from osteochondral tissues obtained from patients with gonarthrosis. Cell viability, toxicity and proliferation and levels of stage-specific embryonic antigen-1, a precursor to human prechondrocytes, were evaluated spectrophotometrically. The results from the untreated control group were compared with those of the study groups, where naproxen was administered in varying doses (1-1,000 µM). Surface morphologies of the cells were compared using inverted light and environmental scanning electron microscopy. Treatment groups were compared by analysis of variance with Tukey's honest difference post hoc test. P<0.01 was considered to indicate a statistically significant difference. The research revealed significant changes to proliferation and differentiation of chondrocytes in all treatment groups (P<0.01). Naproxen was demonstrated to suppress chondrocyte proliferation and differentiation, which may be an important factor to consider when prescribing this medication to patients.

Remote Cerebellar Haemorrhage Occurring after Transcranial Pituitary Surgery.

Post supratentorial and spinal surgeries, in rare cases, Remote Cerebellar Haemorrhage (RCH) develops as a complication. Although the exact aetiology of RCH remains uncertain, excessive drainage of the Cerebrospinal Fluid (CSF) is accepted as the most possible cause. It has been suggested that overdrainage of CSF leads to stretching and resultantly tearing of the cerebellar veins. Early diagnosis and appropriate management decrease mortality and morbidity significantly. In this report, we present a case of RCH encountered on the third postoperative day of transcranial pituitary surgery and discuss the possible causative factors. Excessive loss of CSF is considered to be the major cause of RCH. To our knowledge this is the first case of RCH seen after transcranial macroadenoma surgery reported in the literature so far.

Forestier syndrome presenting with dysphagia: case report of a rare presentation.

Diffuse idiopathic skeletal hyperostosis (DISH) (Forestier syndrome) is a rheumatologic disease, the etiology of which is not exactly known. It is characterized by spinal osteophyte formations resulting from the ossification of the paravertebral ligaments and muscles. Anterior longitudinal ligament is the usual site of involvement and the frequency of the disease increases after the 5th decade. Lower cervical segments are the most frequently involved regions whereas the upper cervical involvement leading to dysphagia is very rare. In this report, a 77-year-old patient with Forestier syndrome in upper cervical region presenting with dysphagia was presented. Anterior cervical osteophyte resection was performed with no need for discectomy, fusion or stabilization. The patient showed a significant improvement in his all preoperative symptoms, and no recurrence was detected at 1-year follow-up.

Rapidly progressing interhemispheric subdural empyema showing a three-fold increase in size within 12 hours: Case report.

BACKGROUND: Subdural empyema is a rare form of intracranial infection. It is described as accumulation of purulent infective material between the inner layer of dura mater and outer layer of arachnoid membrane. CASE DESCRIPTION: A 17-year-old girl was admitted to the emergency department with acute left hemiplegia and was diagnosed with interhemispheric subdural empyema that showed a three-fold increase in size within 12 hours. Complete recovery was achieved with emergency surgical evacuation and additional 3 weeks of antibiotic treatment. CONCLUSION: Subdural empyema should be diagnosed and managed early in time since it may progress very rapidly and can cause high morbidity and mortality. Complete recovery can be achieved if it is diagnosed early and treated in time.

The Effect of Matrix Metalloproteinase-3 on the Prognosis and Biological Behaviour of Meningiomas.

AIM: To analyse the effect of MMP-3 (Matrix Metalloproteinase Enzyme-3)-one of the extracellular matrix proteins- on the prognosis and biological behaviour of meningiomas. MATERIAL AND METHODS: 79 cases of meningioma that were operated in our clinic between 2005 and 2010 were retrospectively analysed. Age, sex, preoperative peritumoral edema, histological subtype, grade, Ki-67 expression, MMP-3 staining pattern and recurrence rate were analysed. Pathological preparations were graded according to the WHO (World Health Organisation) 2007 grading system. RESULTS: Of the MMP-III positive cases; 24 cases (60%) were grade I, 16 cases were grade II. The MMP-3 staining pattern was significantly positive (80%) in grade II meningioma. 14 of the MMP-3 positive cases were atypical meningiomas. Of the 20 cases with high Ki-67 proliferation index (PI), 12 cases (60%) were MMP-3 positive and 8 cases (40%) were MMP-3 negative. Rates of recurrence and preoperative peritumoral edema were high in cases with MMP-3 positivity. CONCLUSION: In this study it was determined that MMP-3 positivity has a strong relationship with meningiomas having an aggressive character. MMP-3 may be used as a proliferation marker for biological behaviour, recurrence rate and prognosis of meningiomas.

Intraabdominal Pseudocyst Developed after Ventriculoperitoneal Shunt: A Case Report.

Abdominal pseudocyst is a rare complication developing after ventriculoperitoneal shunt treatment. It is more commonly seen particularly in children. The underlying pathogenesis may be associated with repeat revisions or infections. Morphologically, it has no complete cyst wall, presenting only with a pseudocapsule among the intestinal loops, around the lower shunt tip. The principal problem appears to be the reduced peritoneal absorption capacity. The treatment is complicated and difficult. In this report, we present an 8-year-old abdominal pseudocyst case with a history of many shunt revisions.

Comparison of the Surgical Results for Foramen Magnum Decompression with and without Duraplasty in Chiari Malformation Type 1.

AIM: The surgical results for foramen magnum decompression (FMD) with and without duraplasty in Chiari Malformation type 1 (CM-1) were compared retrospectively. MATERIAL AND METHODS: Thirty-nine cases of CM-1 with and without syringomyelia (SM) were included. There were 18 patients in the nonduraplasty and 21 in the duraplasty group. Syringomyelia, tonsillar herniation (TH), preoperative symptom duration, and postoperative SM size were compared. RESULTS: No significant difference was found between improvement in the duraplasty group (81%) and the non-duraplasty group (61.1%). In cases whose symptom duration was 0-36 months, improvement in the duraplasty group (93%) was significantly better than in the nonduraplasty group (50%) (p < 0.01). The rate of syrinx regression was 92.3% in the duraplasty group and 12.5% in the non-duraplasty group (p < 0.05). In cases with SM, the improvement was 21.4% in the non-duraplasty group compared to 78.6% in the duraplasty group (p=0.056). In cases with TH greater than 10 mm, the improvement was 66.7% in the non-duraplasty group, whereas all six cases (100%) in the duraplasty group had improved. CONCLUSION: In SM associated cases, cases with TH greater than 10 mm, and whose symptom duration is less than 36 months, duraplasty is a more reliable choice despite a slightly higher rate of complications.