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Among the countless endeavours made at elucidating the pathogenesis of COVID-19, those aimed at the histopathological alterations of type 2 alveolar epithelial cells (AT2) are of outstanding relevance to the field of lung physiology, as they are the building blocks of the pulmonary alveoli. A merit of high regenerative and proliferative capacity, exocytotic activity resulting in the release of extracellular vesicles (EVs) is particularly high in AT2 cells, especially in those infected with SARS-CoV-2. These AT2 cell-derived EVs, containing the genetic material of the virus, might enter the bloodstream and make their way into the cardiovascular system, where they may infect cardiomyocytes and bring about a series of events leading to heart failure. As surfactant protein C, a marker of AT2 cell activity and a constituent of the lung surfactant complex, occurs abundantly inside the AT2-derived EVs released during the inflammatory stage of COVID-19, it could potentially be used as a biomarker for predicting impending heart failure in those patients with a history of cardiovascular disease.

In this study, magnetic spinel copper ferrite (CuFe2O4) nanostructures were eco-friendly synthesized using Nasturtium officinale extract. Physicochemical properties of these nanostructures were determined by transmission electron microscopy, field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), vibrating sample magnetometry, and energy dispersive X-ray mapping analysis. XRD patterns conform to the CuFe2O4 formation. SEM results demonstrated ceramic spinel CuFe2O4 nanostructures with spherical surface morphologies. The cytotoxicity effect of CuFe2O4 nanostructures against rat pheochromocytoma (PC12) cells was evaluated based on MTT assay. The magnetic nanostructures had low toxicity at a concentration of 250 µg/mL. It appears that these nanostructures can be considered as suitable candidates for drug delivery and other biomedical applications, because of their low toxicity effects.

Objective Chordomas are uncommon primary malignant tumours that have a high rate of recurrence. They are thought to form along the spine from remains of the embryonic notochord. Treatment for recurrent tumours is complicated and contentious.They are unresponsive to conventional chemotherapy and radiotherapy. Chordomomas simply lack a viable chemotherapeutic standard. Throughout the fetus's development, the Sonic Hedgehog (SHH) pathways connecting a variety of processes involved in tissue and organ expansion and differentiation. To investigate the role of signalling the hedgehog in recurrent spinal chordomas, immunohistochemistry was used to identify SHH and GLI1 levels. In situ hybridization was also used to differentiate PTCH1 and GLI1 expressions. Methods From 1997 to 2020, we looked at 23 paraffin-embedded recurrent spinal chordoma samples from 23 patients (9 men, 14 women; median age: 63 years). All the patients were treated at the University Medical Center Goettingen in Germany and Azad University of Medical Sciences in Tehran, Iran. This study only included patients who had been diagnosed with conventional chordoma. Results SHH expression (+) and GLI1 expression were discovered in all 23 cases (+) immunohistochemically. GLI1 and SHH levels were markedly increased by recurrent spinal chordoma scores. In the recurrent spinal chordoma, in situ hybridization demonstrated positive responses for PTCH1 and GLI1. Conclusion The Shh sample that represents is believed to play a role in spinal chordoma recurrence.The increased amounts of SHH and GLI1 activity in all chordoma samples, according to the study, indicate an autocrine ligand-dependent activation of the conventional HH signalling cacade. It's hard to rule out a non-canonical or paracrine pathway. Hedgehoginhibitors, such as SHH- and GLl-inhibitors, are believed to be associated in our findings, could be a promising approach for treating recurrent spinal chordomas.

Recent studies on the pathophysiology of COVID-19 are indicating that the Angiotensin convertase enzyme 2 (ACE-2) and transmembrane serine protease 2 (TMPRSS2) can act as a major component in the fusion of SARS-Cov-2 with target cells. It has also been observed that the expression of ACE-2 and TMPRSS2 can be altered in malignancies. Shedding light on this matter could be crucial since the COVID-19 pandemic interfered with many gastrointestinal cancer screening programs. Herein we discuss the possibility of severe forms of COVID-19 in patients with gastrointestinal cancers due to the gastrointestinal entry route of SARS-CoV-2 into the human body. The disruption of cancer screening programs caused by the current COVID-19 pandemic could therefore have massive negative health impact on patients affected by gastrointestinal malignancies.

In the current study, Methylation and expression microarray data related to Schizophrenia (SCZ) were analyzed to identify genes whose aberrant promoter methylation could play a crucial role in the dysregulation of gene expression. After data analysis, two genes including KLF9 and MYH11 were identified. Considering CpG sites in the promoter region of the mentioned genes using Methprimer database, Bisulfite specific primer (BSP) was designed, and Methylation specific-high resolution melting (MS-HRM) analysis was performed to assess the promoter methylation status of the genes, and also real-time PCR was used to evaluate mRNA expression level of KLF9 and MYH11 in 50 SCZ and healthy control specimens. The results show 62% hypermethylation and 38% hypomethylation of KLF9 in SCZ samples and 34% hypermethylation and 66% hypomethylation in healthy control samples. MYH11 promoter shows 54% hypermethylation and 46% hypomethylation in SCZ samples while 28% hypermethylation and 72% hypomethylation in healthy controls. The result of real-time PCR shows downregulation of KLF9 and MYH11 in SCZ samples compared with healthy samples. The aberrant methylation has a direct effect on the expression of mentioned genes.

Since thermo-chemotherapy was suggested as an effective treatment for gastric cancer, we aimed to evaluate the effects of hyperthermia combined with cisplatin (DDP) on the inhibition of human gastric cancer drug-resistant cells in vitro and explore its possible mechanisms.SGC-7901/DDP cells were cultured and divided into control, cisplatin, hyperthermia, and hyperthermia combined with cispla- tin groups. Hyperthermia was done at 42°C, 44°C, 46°C, 48°C, and 50°C for 12 h, 24 h, 36 h; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl- 2H-tetrazolium bromide (MTT) assay detected the proliferation of SGC-7901/DDP at different time and temperature, and the apoptotic rate of SGC-7901/DDP cells was evaluated by using Annexin staining assay. High-throughput Chromatin immunoprecipitation (ChIP)- seq was applied to test long non-coding RNA expression in SGC-7901/DDP cells. Then, real-time fluorescence quantitative polymerase chain reaction was used to verify the expression of long non-coding RNA in all groups.Double staining showed that hyperthermia combined with cisplatin increased the rate of early apoptosis of SGC-7901/DDP cells. Long non-coding RNA high-throughput ChIP-seq showed a significantly larger amount of long non-coding RNAs and mRNAs in the cells treated with hyperthermia combined cisplatin group in comparison with the control group. We observed that the upregulated mRNAs and long non-coding RNAs were highly related to immune system response and CD95 signaling pathway in nucleus, and down- regulated mRNAs and long non-coding RNA were highly related to Mammalian target of rapamycin (mTOR) and Tumor necrosis factor (TNF) receptor signaling pathway in cytoplasm.Hyperthermia combined with cisplatin reversed the expression of a large number of mRNAs and long non-coding RNAs in human gastric cancer drug-resistant cells. The molecular mechanism of inhibiting the proliferation of human gastric cancer drug- resistant cells may be related to the upregulation of long non-coding RNAs and mRNAs contributed in CD95, mTOR, and TNF receptor signaling pathway.

Sedentary lifestyle and dyslipidemia are well-recognized risk factors for cardiovascular diseases (CVD). Changes in blood lipid profile (total cholesterol (TC), triglycerides, high-density lipoprotein [HDL], and low-density lipoprotein [LDL]) due to the exercise may be beneficial for decreasing CVD-related events. In this review we aimed to investigate the effect of different types of exercise on lipid profile components in people with different health conditions and age ranges. A systematic search was performed covering PubMed, Web of Science, and Google Scholar for English articles from 2010 until November 2021. Finally, 31 studies were included in our study. Results showed that exercise in younger individuals sometimes resulted in no significant changes of any of the variables or some of them; however, efficient improvement was observed in all studies of older and middle-age groups. In terms of health condition and gender; healthy individuals, overweight people, subjects with type 2 diabetes and obesity, and male participants found to have benefited more from the exercise. In patients with chronic kidney diseases lipid profile improvement was not significant. The cardiac rehabilitation program, particularly comprehensive cardiac rehabilitation, proved to be more beneficial than exercise alone in the case of cardiovascular patients and those at elevated risk of CVD. In conclusion exercise is beneficial in terms of improving lipid profile but for younger population, and those with kidney problems and CVD patients, more further preparations are needed under the supervision of experts in the field of sports and medicine to achieve the desired result. Also, more studies are needed for these groups in order to provide a definite and reliable conclusion.

Background: Previous studies have shown that social isolation stress (SIS) could associate with several systemic diseases; however, the role of SIS on liver dysfunction has yet to be established. This study aimed to investigate the effect of SIS on liver function and possible drug toxicity through liver inflammation and oxidative stress. Methods: Male Naval Medical Research Institute mice in two groups of SIS and control were treated with typical anti‐depressant and anxiolytic agents including fluoxetine, norfluoxetine, desipramine, and imipramine in both groups. Then blood concentrations (or their active metabolites) of these drugs were assessed. Liver function test, including aspartate transaminase (AST), alanine aminotransferase (ALT), total bilirubin, and conjugated bilirubin), oxidative activity, inflammatory cytokines, and the gene expression of cytochrome P450 enzymes were assessed. Results: We observed that the liver enzymes including AST and ALT was slightly higher in SIS animals. The blood concentrations of fluoxetine, norfluoxetine, desipramine, and imipramine were significantly higher in SIS animals. The gene expression of CYP1A2, CYP2A6, CYP2C9, CYP2C29, and CYP2D were significantly decreased in SIS animals. Our results showed that SIS animals had significantly higher level of tumor necrosis factor‐α, interleukin‐1β, and interleukin‐6. SIS could significantly decrease the activity of antioxidant agent (Glutathione). Conclusion: We hypothesized that SIS could induce liver dysfunction and decrease the rate of drug clearance through liver inflammation and oxidative stress; therefore, the blood concentration of anti‐depressant/anxiolytic agents should closely monitor in SIS due to the high toxicity of these agents., In the current study, we hypothesized that social isolation stress could induce liver dysfunction and decrease the rate of drug clearance through liver inflammation and oxidative stress; therefore, which could lead to drug toxicity with anti‐depressants and anxiolytics.

Since the inflammation and oxidative stress is the main pathophysiological pathway of neural damage in spinal cord injury (SCI), we tried to evaluate the role of ivermectin (IVM) combined with multi-walled carbon nanotube (MWCNT) in the treatment settings of SCI and its underlying mechanism. Wistar rats with T9 vertebra laminectomy in five groups of: sham-operated, vehicle, IVM (0.1 mg/kg), IVM-MWCNT (0.1 mg/kg), and minocycline (90 mg/kg) were used. We evaluated the locomotor scaling and other behavioral tests for neuropathic pain. Also, tissue samples were obtained to evaluate the expression of M1 and M2 macrophage marker, concentration of TNF-α, IL-1β, and IL-1, and oxidative stress level to assess neuroinflammatory changes. Both IVM and IVM-MWCNT after induction of SCI significantly enhanced the experimental tasks’ outcomes, including locomotion and neuropathic tests. Also, decreasing in pro-inflammatory cytokines including TNF-α, IL-1β, and IL-1 in the spinal cord and dorsal root ganglion tissues was also notable in both IVM and IVM-MWCNT-treated groups 28 days after induction of SCI in compared to the vehicle-treated SCI group. Both IVM and IVM-MWCNT significantly decreased oxidative stress, induced by SCI, based on the results of ROS and NADPH activity. IVM-MWCNT-treated animals indicated better outcome in every previous experiment in comparison to IVM-treated animals. The effectiveness of IVM-MWCNT was similar to minocycline treatment in all experimental task (as positive control group). IVM-MWCNT might be a novel treatment in spinal cord injury, which could act through decreasing the oxidative stress and increase the polarization of M1 in comparison to M2 macrophages., Spinal cord injury, Ivermectin, Care setting, Oxidative stress, M1 macrophage, M2 macrophage.

Purpose: In the current study, we tried to analyze the diagnostic value of HSP90α expression during the course of disease in patients treated with and without surgery. Methods: Three hundred and twelve patients with lung cancer who referred to Qinhuangdao First Hospital from June 2016 to March 2021 were selected as the experimental group and 160 healthy individuals subjected as the control group in this cohort study. The ELISA method was used to detect the expression level of plasma HSP90α. Results: We observed significant differences in the level of HSP90α in pathologic type, differentiation degree, stage, and presence of lung, liver, and bone metastasis; HSP90α was significantly higher in non-small cell lung carcinoma in comparison with small cell lung carcinoma, especially in lung adenocarcinoma. Our results demonstrated that HSP90α at 71.45 ng/mL had a sensitivity of 66.3% and a specificity of 95.0% for diagnosing lung cancer. Also, we observed that the HSP90α expression was significantly increased prior to lung cancer relapse in patients treated with chemoradiotherapy and surgery. Conclusion: Serum level of plasma HSP90α could be a reliable biomarker in diagnosing lung cancer and its subtypes and might be a valid biomarker for predicting lung cancer relapse in patients treated with chemoradiotherapy and surgery.

Povidone-iodine (PVI) is an effective disinfection solution for surgical wounds. However, there is some reports of its adverse effects on wound healing and bone reunion. Here, we evaluate the efficacy and safety of PVI irrigation in the prevention of surgical site infection in spinal surgery.

OncomiRNAs involved in human colorectal cancer (CRC) are capable of suppressing the expression of their targets via cleavage or translational arrest. Therefore, an improved understanding the functions of these oncomiRNAs and the molecular pathways in CRC development that they are involved in will assist in the manipulation of miRNAs, providing a novel therapeutic approach against CRC. In this review, we provide a particular perspective of miRNAs implicated in the progression of CRC. We describe an interaction network of CRC-associated miRNAs and their targets involved in tumor growth, proliferation, migration/invasion, epithelial-to-mesenchymal transition (EMT) formation, metastasis, and anticancer resistance. Additionally, the therapeutic potentials of these miRNAs in CRC are fully discussed. Thus, key oncogenic miRNAs involved in progression and metastasis of CRC (e.g., miR-181a/b, miR-135a/b, miR-150 and miR-150-5p, miR-155, miR-181b, miR-200 a/c, miR-22, miR-106a, hsa-miR-103a, hsa-miR-1827, miR-135b, miR-150 and miR-150-5p, miR-181b, and let-7f-5p) are considered in this review. Furthermore, proangiogenic and antiapoptotic miRNAs, their molecular regulatory networks, biological functions, and target genes are also discussed. An in-depth understanding of the molecular mechanisms underlying the regulation of miRNAs will increase the knowledge of miRNA regulatory function in the progression of CRC and promote the development of novel therapeutic measures.

Carcinosarcomas are tumors comprising part adenocarcinoma and part sarcoma; the presence of carcinosarcoma in the head-and-neck region is very rare. These tumors are typically highly aggressive (G3) and arise most frequently from the salivary gland. Here, we present a case report on a brain metastasis as the primary manifestation of a carcinosarcoma. Magnetic resonance imaging showed a tumor of the pineal region with infiltration of the brainstem and the corpus. The staging following the histopathological diagnosis revealed the origin of the tumor in the left parotid gland. We present an overview of the significance of published treatment strategies in carcinosarcoma.

In low back pain management surgery is currently commonly used with a new technique called minimally invasive discectomy, while open discectomy is still preferable in many cases. In this regard, the efficacy of tubular discectomy (TD) were compared with conventional standard lumbar disc procedure (conventional microdiscectomy). This study was performed as a clinical trial conducted on patients who were under TD and conventional microdiscectomy using unilateral retractor at Bou Ali, Mehrad, Laleh Hospitals during the years 2001 to 2017. The pain score was determined based on the use of Visual Analogue Scale (VAS). The Roland Morris Disability Questionnaires (RMQ) and mean Oswestry disability index (ODI) were also calculated. Our findings revealed that the two groups were similar in terms of demographic characteristics (age, sex, body mass index, etc.) (p> 0.05). The findings indicated the superiority of TD over the classic approach. The mean scores of ODI in conventional microdiscectomy and TD groups were reported as 12.53 ± 7.09 and 9.51 ± 7.83, respectively. ODI revealed that patients with TD surgery had less disability in lifting objects, sitting, standing, and traveling. In the conventional microdiscectomy group, 12 (20%) patients were affected by complications of surgery, but no complication was reported in any patient with TD (p = 0.000). The mean index of Roland Morris disability in the conventional microdiscectomy and TD groups were estimated to be 6.033 ± 2.98 and 3.73 ± 3.25 (p = 0.000). However, both groups did not differ in terms of visual scores for pain and relapse (p > 0.05). Our study demonstrates that disease relapse within 6 months after the surgery, the RMQ and the ODI values were significantly better in TD than the other group.

Chordomas is rare malignant bone tumors thought to arise from remnants of embryonic notochord along the spine, frequently at the skull base and sacrum. Although chordoma is slow growing tumors, while are extremely recurrent, and aggressive, as well as the rate of prognosis remains poorly. Radical surgery and high-dose radiation are the most used treatments. Currently, there is no effective chemotherapeutic standard for chordomas. The Hedgehog (HH) pathway adjusts various processes included in expansion and differentiation of tissues and organs throughout the fetus&rsquo, s life, furthermore cell growth and differentiation in the adult organism, of the cell in an adult organism, in which acute anesthesia is involved in multiple cancers. To study the role of signaling the hedgehog in the base of the skull and sacrum chordomas, the expression of SHH and GLI-1 levels were detected immuno histochemically, Additionally, PTCH-1 and GLI-1 expressions were distinguished by in- Situ- hybridization. Based on the findings presented herein, it is likely that the HH signal cascade was revealed even in cranial, where consecoently spinal chordoma and their recurrences play an important role. Our staining exhibited a canonical, ligand- dependent and autocrine Hedgehog signaling in skull base and sacrum chordomas including relapse. Due to the high levels of SHH and GLI-1 expression in all investigated chordoma samples, the study suggests a possible autocrine ligand-dependent activation of the canonical HH signaling cascade. A paracrine or non-canonical pathway cannot be excluded. Our results suggest that Hedgehog-inhibitors, like SHH-, GLI- and SMO- inhibitors, might serve as a potential and effective target for the treatment of chordomas.

Background and Study Aims In microvascular decompression of the trigeminal nerve for trigeminal neuralgia (TN), the site of conflict is occasionally difficult to identify. Endoscopy has been described to better evaluate the anatomical conflict in such situations. We hypothesized that indocyanine green (ICG) angiography could allow for better visualization of the compressing artery and its anatomical relation to the nerve. Material and Methods ICG angiography was performed in 17 TN patients undergoing microvascular decompression. We focused on whether ICG angiography is helpful in determining the site of conflict, particularly when not directly visible via the microscope, and whether fluorescence is strong enough to shine through the nerve obliterating the direct view of the compressing vessel. Results In four patients, the site of conflict was immediately apparent after opening the cerebellopontine cistern, and ICG angiography did not provide the neurosurgeon with additional information. In another two patients, imaging quality and fluorescence were too poor. Of the remaining 11 patients with a hidden site of nerve–vessel conflict, ICG angiography was found to be helpful in anticipating the site of compression and the course of the artery in 7 patients, particularly in regard to the so-called shining-through effect through fiber bundles of the thinned nerve. Of all the patients, 88% reported at least improvement or cessation of their symptoms, including all of the patients with a shine-through effect. Conclusion ICG angiography could be a helpful adjunct in decompressing the trigeminal nerve and can guide the surgeon to the nerve–vessel conflict. Intensity of the fluorescence is powerful enough to shine through thinned and splayed trigeminal nerve fiber bundles.

Background:Vertebroplasty has become a common treatment for relieving pain in osteoporotic vertebral fractures. However, there is contradictory evidence regarding its efficacy. The aim of this study was to determine the degree of pain relief offered by percutaneous vertebroplasty in the treatment of osteoporotic vertebral compression fractures (OVCFs) in patients with or without an intravertebral cleft. Material and Methods: In this multicenter, randomized, placebo-controlled trial all patients who had one or multiple painful, unhealed compression fractures were randomly assigned to undergo vertebroplasty or a sham procedure. The patients in the vertebroplasty group were divided into two subgroups: A - with intravertebral cleft, and B - without intravertebral cleft. They were followed up for the mean pain reduction assessed by visual analogue scale (VAS), and changes in the quality of life using the osteoporosis and Roland-Morris disability questionnaire scores (RDQ) at 1, 6, and 12 months, and two years after the procedure. Results: A total of 1,311 patients were studied (vertebroplasty 661, sham 650). The data showed that those with intravertebral clefts had significantly less severe back pain (p = 0.01) and functional disability (p=0.03) at month 12 compared to those without intravertebral cleft. However, the study groups did not differ significantly with respect to the pain score or the RDQ score at other measurement points (p>0.05). There was a trend in the RDQ score toward less pain in patients with filled clefts compared with patients without clefts after one and two years after surgery, this difference did not approach statistical significance. Conclusion: We found no significant benefit of percutaneous vertebroplasty (PVP) over a sham procedure in patients with vertebral compression fractures with or without vertebral clefts 6 months after surgery. One and two years after surgery, there was a trend toward less pain.

BACKGROUND: Gunshot wounds and blast injuries to the upper limbs produce complex wounds requiring management by multiple surgical specialities. AIM: We sought to determine the pattern of peripheral nerve injuries among Iraqi soldiers in the war. METHODS: We performed a 3 year retrospective cohort analysis based on medical records of patients with sustaining gunshot wounds and blast injuries to the upper limbs. Ethical approval was obtained from the institutional review board. The patients included were male, serving military personnel of all age groups and ranks presenting with weakness or sensory loss of radial nerve. Three hundred eighteen patients aged 24 years or older with a high-energy, diaphyseal fracture of the humerus and complete motor and sensory radial nerve palsy were reviewed retrospectively. In these patients, the physical examination and electrodiagnostic study were carried out by experienced neurologists. Seddon's classification system was used to assess the severity of the injury. The data related to the types of fracture, the type of damage, the factors causing damage and the failure of treatment were entered into the IBM SPSS 23 software after extraction of files. Based on mid-range indicators and data distribution, traumatic injuries among Iraqi soldiers in the war against ISIL were then investigated. RESULTS: A group of 318 patients with mean age of 25.41 ± 6 years were enrolled in the study, of which 127 patients were included with an open fracture and 191 patients with closed lesions. All 127 patients with a transected radial nerve had an open humerus fracture and were part of a complex upper-extremity injury. 113 of 127 subjects had primary repair of the radial nerve and recovered well. 14 of 127 subjects were not recovered. 3 of them had iatrogenic radial nerve injury due to the internal fixation device. Furthermore, all 191 patients with closed injuries recovered well. The average time to initial signs of recovery was 8 weeks (range, 1–27 weeks). Axonotmesis and Neurotmesis were found in 283 (89%) subjects. The average time to full recovery was determined to be 6 months (range, 1–22 months). The blast was found to be the main cause of nerve injury in 236 (74.2%) cases, followed by gunshot damage (21.4%, 68 subjects), falling from height and motor vehicle accidents (4.4%, 14 subjects) and multiple injuries (17%, 54 cases). CONCLUSIONS: Trauma caused by factors such as explosions and gunshot worsens the condition of the injuries and presents the treatment conditions with many challenges. However, the success rate in post-surgical recovery of humerus fracture and injured radial nerve can be remarkably higher in young people as compared to other age groups.

Background:Patients undergoing spinal surgery while under anticoagulation therapy are at risk of developing bleeding complications, even though lower incidences have been reported for joint arthroplasty surgery. There is a gap in the medical literature examining the incidence of postoperative spinal bleeding in patients who were under anticoagulation medication at the time of surgery. Methods:We prospectively followed a consecutive cohort of 100 patients (58 male, 42 female) undergoing spinal surgery. The average patient age was 48.7 years and the minimum follow up time was 12 months. Diagnosis was lumbar spinal stenosis in 20, herniated lumbar discs in 63, degenerative cervical disc disease in 3, and cervical disc herniation in 14 cases. In our study, platelet aggregation inhibitors (clopidogrel and/or acetylsalicylic acid) were given for the treatment of cardiovascular and cerebrovascular thrombotic events, to reduce risk of stroke in patients who have had transient ischemia of the brain or acute coronary syndrome, and as secondary prevention of atherosclerotic events (fatal or nonfatal myocardial infarction (MI). A cessation of anticoagulants (acetylsalicylic acid or clopidogrel) in our patients in the peri- and postoperative period was contraindicated. Results:Sixty-three patients were on both clopidogrel and acetylsalicylic acid and 37 on acetylsalicylic acid only. None of the patients suffered any postoperative bleeding complication. Three patients suffered postoperative wound dehiscence and one patient had an infection that required reoperation. Conclusion:The question of whether preoperative platelet aggregation inhibitors must be stopped before elective spinal surgery has never been answered in the literature. In our prospective series, we have found no increase in the risk of postoperative spinal bleeding with the use of clopidogrel or acetylsalicylic acid. This finding suggests that spine surgery can be done without stopping anticoagulation. Lacking specific guidelines, each patient should be treated on an individual basis, and the potential benefits of anticoagulation should be compared with the potential risks (risk–benefit ratio). peerReviewed

To clarify whether vascular endothelial growth factor receptor 2 (VEGFR2) and inducible nitric oxide synthase (iNOS) are involved in the angiogenesis and recurrence of spinal chordoma tissues and influence the overall survival. All patients affected by a spinal chordoma surgically treated between 1986 and 2007 were reviewed. We examined the expression of VEGFR2 and iNOS with immunohistochemistry using a tissue microarray containing 120 chordoma samples. Local recurrence and overall survival (OS) were analyzed. A series of 40 chordoma patients who underwent surgery for a total of 120 lesions (including 80 recurrent lesions) were identified (sacrum 77.5 %, lumbar spine 17.5 %, cervical/thoracic spine 5 %). Surgical margins were wide in 30 (75 %), marginal in 8 (20 %) and intralesional in 2 (5 %) patients. Median follow-up was 120 months. The 5- and 10-year OS of the entire series of patients was 78.6 and 30 %, respectively. There were five primary chordomas (12.5 %) with moderate and 35 (87.5 %) with strong expression of VEGFR-2. All recurrent spinal chordomas displayed strong expression of VEGFR-2. The expression of iNOS was predominately moderate to high in primary chordomas: There were 15 tumors (37.5 %) with moderate and 25 tumors (62.5 %) with strong expression. All recurrent chordomas displayed strong expression of iNOS. The high expression of VEGFR-2 and iNOS affected the OS. The OS at 10 years was only 30 %.

Chordomas are locally invasive tumors that have a tendency to relapse despite optimal treatment. Specific biological markers might be used to describe their behavior. There is currently no agreement regarding the best way to manage intracranial chordomas. We studied the expression of vascular endothelial growth factor receptor 2 (VEGFR-2), inducible nitric oxide synthase (iNOS), and Ki-M1P in 145 paraffin-embedded tumors. The purpose of our study was to determine: (a) the role of potent angiogenic factors VEGFR-2 and iNOS and their relationship to each other in skull base chordoma and (b) the role of monocytes/macrophages as a potential iNOS source in the angiogenic process. A series of 74 chordoma patients for a total of 145 lesions (including 71 recurrent lesions) and 10 specimens from embryonic notochord were investigated for the expression of iNOS, VEGFR-2, Ki-M1P, and CD-34 using immunohistochemistry. In the majority of the chordomas, correlations were found between iNOS and the immunoreactivity of Ki-M1P (r = 0.5303, P