MGMT Gene rs1625649 Polymorphism in Iranian Patients with Brain Glioblastoma: A Case Control Study.

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor with poor prognosis and high potential of dispersion to other brain tissues in adult. Effective and modern choices of treatment including chemotherapy with alkylating agents marginally extend survival of GBM. However, alkylating agents can lead to highly harmful mismatch during DNA replication causing apoptosis and cell death. Accordingly, O6-Methylguanine-DNA methyltransferase (MGMT) removes alkyl adducts, thereby causing resistance to alkylating drugs. Single-Nucleotide Polymorphisms (SNPs) in MGMT promoter region may play a role in the regulation of MGMT expression and prediction of glioma development risk. In order to evaluate the clinical significance of rs1625649 SNP in the MGMT promoter region of glioblastoma, genomic DNA from a series of 54 patients with GBM and 50 healthy individuals in Iranian population were collected for tetra ARMS PCR amplification. None of the "A" or "C" alleles were associated with tumor occurrence, the "AA" genotype was more frequent in healthy subjects, and the "AC" genotype was 4.6 times more common in patients with GBM. The longest survival time was observed in the "CC" genotype; however, this difference was not statistically significant. On the other hand, homozygous rs1625649 (AA genotype) was significantly associated with a better survival than the cases with heterozygous rs1625649 (CA genotype) or wild type rs1625649 (CC genotype), predicting better response to temozolomide-based chemotherapy.

VEGF gene polymorphisms in Iranian patients with intracranial glioblastoma.

BACKGROUND: Glioblastoma is one of the most common malignant brain tumors in adults with poor prognosis. Neovascularization is one of the characteristics of these tumors, which is associated with overexpression of vascular endothelial growth factor (VEGF). Accordingly, single nucleotide polymorphisms of this gene could play an important role in structural and functional alterations leading to overexpression of this gene in GBM. METHODS: A total number of 49 patients with GBM and 50 healthy controls were included in the current study. The Genomic DNA was extracted from brain tumor/tissue samples, and after purification assessment, the alleles, and genotypes of rs3025039 and rs2010963 polymorphisms of the VEGF gene were investigated using T-ARMS-PCR. RESULTS: The "T" allele of rs3025039 was 2.79 times more frequent in GBM patients compared to controls (P=0.01). Moreover, the "CT" genotype was 2.83 times more common among patients (P=0.015), while the "CC" was more frequent in controls (P=0.009). The mean overall survival was significantly different between three genotypes of rs3025039, with the longest survival time in "CT" genotype (15.10±5.21, P=0.041). Besides, rs2010963, was significantly associated with GBM occurrence, with the "G" allele being 1.96 times more frequent in patients (P=0.01), as well as the "GG" genotype, which was 7.87 times more common in patients (P<0.001). CONCLUSIONS: Polymorphisms of VEGF could potentially play a role in pathogenesis of GBM, as the allele and genotype distributions of rs3025039 and rs2010963 SNPs were significantly associated with GBM occurrence.

Complete Versus Incomplete Surgical Resection in Intramedullary Astrocytoma: Systematic Review with Individual Patient Data Meta-Analysis.

STUDY DESIGN: Systematic reviewBackground: Considering the infiltrative nature of intramedullary astrocytoma, the goal of surgery is to have a better patient related outcome. OBJECTIVE: To compare the overall survival (OS) and neurologic outcomes of complete vs incomplete surgical resection for patients with intramedullary astrocytoma. METHODS: A comprehensive search of MEDLINE, CENTRAL and EMBASE was conducted by two independent reviewers. Individual patient data (IPD) analysis and multivariate Cox Proportional Hazard Model was developed to measure the effect of surgical strategies on OS, post-operative neurological improvement (PNI), and neurological improvement in the last follow up (FNI). RESULTS: We included 1079 patients from 35 studies. Individual patient data of 228 patients (13 articles) was incorporated into the integrative IPD analysis. Kaplan-Meier survival analysis showed complete resection (CR) significantly improved OS in comparison with the incomplete resection (IR) (log-rank test, P = .004). In the multivariate IPD analysis, three prognostic factors had significant effect on the OS: (1) Extent of Resection, (2) pathology grade, and (3) adjuvant therapy. We observed an upward trend in the popularity of chemotherapy, but CR, IR, and radiotherapy had relatively stable trends during three decades. CONCLUSION: Our study shows that CR can improve OS when compared to IR. Patients with spinal cord astrocytoma undergoing CR had similar PNI and FNI compared to IR. Therefore, CR should be the primary goal of surgery, but intraoperative decisions on the extent of resection should be relied on to prevent neurologic adverse events. Due to significant effect of adjuvant therapy on OS, PNI and FNI, it could be considered as the routine treatment strategy for spinal cord astrocytoma.

A minimum data set for traumatic brain injuries in Iran.

PURPOSE: Traumatic brain injury (TBI) is one of the major public health concerns worldwide. Developing a TBI registry could facilitate characterizing TBI, monitoring the quality of care, and quantifying the burden of TBI by collecting comparable and standardized epidemiological and clinical data. However, a national standard tool for data collection of the TBI registry has not been developed in Iran yet. This study aimed to develop a national minimum data set (MDS) for a hospital-based registry of patients suffering from TBI in Iran. METHODS: The MDS was designed in 2 phases, including a literature review and a Delphi study with content validation by an expert panel. After the literature review, a comprehensive list of administrative and clinical items was obtained. Through a two-round e-Delphi approach conducted by invited experts with clinical and research experience in the field of TBI, the final data elements were selected. RESULTS: A MDS of TBI was assigned to 2 parts: administrative part with 5 categories including 52 data elements, and clinical part with 9 categories including 130 data elements. CONCLUSION: For the first time in Iran, we developed a MDS specified for TBI consisting of 182 data elements. The MDS would facilitate implementing a TBI's national level registry and providing essential, comparable and standardized information.

A systematic review on the recurrence of SARS-CoV-2 virus: frequency, risk factors, and possible explanations.

BACKGROUND: Since late 2019, SARS-CoV-2 which leads to coronavirus disease 2019 (COVID-19), has caused thousands of deaths. There are some pieces of evidence that SARS-CoV-2 genome could be re-detectable in recovered patients. METHODS: We performed a systematic review in the PubMed/Medline database to address the risk of SARS-CoV-2 recurrence. The last update was for 20 November 2020. Among the 1178 initially found articles, 66 met the inclusion criteria and were considered. FINDINGS: In total, 1128 patients with at least one-time recurrence of SARS-CoV-2 were included. Recurrence rate has been reported between 2.3% and 21.4% in cohort studies, within a mean of 20 (ranged 1-98) days after discharge; younger patients are being affected more. Following the second course of disease, the disease severity decreased or remained unchanged in 97.3% while it increased in 2.6%. Anti-SARS-CoV-2 IgG and IgM were positive in 11-95% and 58.8-100%, respectively. Based on the literature, three possibilities include reactivation of previous disease, reinfection with the same virus, and false negative, which have been discussed in details. CONCLUSION: There is a relatively notable risk of disease recurrence in previously recovered patients, even those who are immunised against the virus. More studies are required to clarify the underlying cause of this phenomenon.

Biofluid Biomarkers in Traumatic Brain Injury: A Systematic Scoping Review.

Emerging evidence suggests that biofluid-based biomarkers have diagnostic and prognostic potential in traumatic brain injuries (TBI). However, owing to the lack of a conceptual framework or comprehensive review, it is difficult to visualize the breadth of materials that might be available. We conducted a systematic scoping review to map and categorize the evidence regarding biofluid-based biochemical markers of TBI. A comprehensive search was undertaken in January 2019. Of 25,354 records identified through the literature search, 1036 original human studies were included. Five hundred forty biofluid biomarkers were extracted from included studies and classified into 19 distinct categories. Three categories of biomarkers including cytokines, coagulation tests, and nerve tissue proteins were investigated more than others and assessed in almost half of the studies (560, 515, and 502 from 1036 studies, respectively). S100 beta as the most common biomarker for TBI was tested in 21.2% of studies (220 articles). Cortisol was the only biomarker measured in blood, cerebrospinal fluid, urine, and saliva. The most common sampling time was at admission and within 24 h of injury. The included studies focused mainly on biomarkers from blood and central nervous system sources, the adult population, and severe and blunt injuries. The most common outcome measures used in studies were changes in biomarker concentration level, Glasgow coma scale, Glasgow outcome scale, brain computed tomography scan, and mortality rate. Biofluid biomarkers could be clinically helpful in the diagnosis and prognosis of TBI. However, there was no single definitive biomarker with accurate characteristics. The present categorization would be a road map to investigate the biomarkers of the brain injury cascade separately and detect the most representative biomarker of each category. Also, this comprehensive categorization could provide a guiding framework to design combined panels of multiple biomarkers.

Telemetric Intracranial Pressure Monitoring: A Systematic Review.

Telemetric intracranial pressure (ICP) monitoring is a new method of measuring ICP which eliminates some of the shortcomings of previous methods. However, there are limited data on specific characteristics, including the advantages and disadvantages of this method. The main aim of this study was to demonstrate the indications, benefits, and complications of telemetric ICP monitoring. PubMed, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for relevant studies without language or date restriction in May 2019. Human studies in which telemetric ICP monitoring was the main subject of the study were included. Our initial search resulted in 1650 articles from which 50 studies were included. There were no randomized controlled trials. The majority of the studies were case reports or case series (68%). The most common aim of studies was testing of the device (52%), and monitoring the disease progression or recovery (46%). The most common indications for telemetric ICP monitoring in these studies were testing cerebrospinal fluid shunt function (46%), ICP control after the procedure (36%), and diagnosing intracranial hypertension (22%) and hydrocephalus (12%). In total, 1423 brain disease patients had been monitored in studies. The possibility of long-term ICP monitoring as the main benefit was reported in 38 (76%) studies. The associated complication rate was 7.1%. Despite the increasing application of telemetric monitoring devices, studies to evaluate specific characteristics of this method have been infrequent and inadequate. Future research using a higher level of scientific methods is needed to evaluate advantage and disadvantages.