The aim of this study is to investigate the relationship between isocitrate dehydrogenase-1 (IDH1) mutation and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with recurrence-free interval in glioblastoma patients treated with chemoradiotherapies. Clinical data were collected from 82 patients with totally resected glioblastoma and treated with adjuvant therapies from 2014 to 2019. IDH1 mutation was assessed by immunohistochemistry and MGMT promoter methylation was assessed by different sequencing methods. IDH1 mutation was present in 32 cases and 50 cases were IDH1 wildtype; 54 and 28 patients had unmethylated and methylated MGMT promoter, respectively, Of the 82 patients, 62 patients received chemoradiotherapy while 20 patients only received radiation. Approximately, 61% of patients had a tumor recurrence after 1 year, and 39% showed a recurrence before 1 year of treatment. There was no significant relationship between IDH1 mutation and MGMT promoter methylation (p-value = 0.972). Patients with IDH1 mutation and their age <50 years showed a significant difference in recurrence-free interval (p-value = 0.014). Difference in recurrence-free interval was also statistically observed in patients with unmethylated MGMT promoter and treated with chemoradiotherapies (p-value = 0.031), by which they showed a late tumor recurrence (p-value = 0.016). This revealed that IDH1 mutation and MGMT methylation are independent prognostic factors in glioblastoma. Although IDH1-mutant glioblastomas showed late tumor recurrence in patients less than 50 years old, the type of treatment modalities may not show additional beneficial outcome. Patients with unmethylated MGMT and IDH1 mutation, treated with different chemoradiotherapies, showed a late tumor recurrence.

The purpose of the study was to evaluate the impact of country self-citation rate (SCR) among medical specialties in Saudi Arabia, and to assess the impact of self-citations on the country's total cites world ranking in different specialties. MethodsSCImago Journal & Country Rank (SJR) was used to collect data related to all medical specialties in Saudi Arabia for the period 1996-2019. The country SCR for the specialties was correlated with several bibliometric parameters and examined statistically. The specialties that showed a drop in Saudi Arabia's total cites world ranking following the exclusion of self-citations were identified. ResultsThe median country SCR for 46 specialties in Saudi Arabia was 9.5% (range: 4.6-23.1%). The two specialties with the highest country SCR were Public Health (23.1%) and Family Practice (22.9%). Country SCR was significantly higher in the non-clinical specialties compared to clinical specialties (15.3% vs. 9.6%). It did not correlate significantly with any of the examined productivity indices. The exclusion of self-citations resulted in a drop in Saudi Arabia's total cites world ranking in six (13%) specialties only. There was no significant difference between the country's total cites and net total cites world rankings in the specialties. ConclusionsSelf-citation may be appropriate and signify an expansion of the authors' previous work. Country SCR in medical specialties in Saudi Arabia is relatively low and not affected by total documents and total cites. Non-clinical specialties tend to self-cite more. The exclusion of self-citations had minimal effect on Saudi Arabia's total cites world ranking, indicating that country SCR in the specialties is unlikely to impact its international scientific standing. Our findings do not support the argument for eliminating self-citation from citation-based metrics. We believe that more collaborative and global research practices should be encouraged.

Objectives To examine the factors that influence country self-citation rate (SCR) in clinical neurology and to assess the impact of self-citation on the ranking of the top 50 countries. Methods SCImago Journal & Country Rank was used to collect data for the 50 most cited countries in clinical neurology during 1996–2019. Country SCR was correlated with several productivity parameters and examined statistically. Countries that dropped in their ranking after the exclusion of self-citations were identified. Results The median (range) country SCR for the 50 most cited countries was 11.3%. (5.3%- 47%). Country SCR correlated significantly with total citable documents and total cites numbers and rankings. The exclusion of self-citations led to a drop in the ranking of 8(16%) countries only. No significant difference between the total and net total cites rankings was observed. Conclusions Self-citation can be appropriate and reflect an expansion on earlier research. Highly cited productive countries tend to have high country SCR. Excluding self-citations had minimal impact on the ranking of the top 50 countries. Our findings indicate that self-citation is unlikely to influence country standing amongst the top 50 and does not support the argument for eliminating self-citations from citation-based metrics. A more globalization through international collaboration in research is encouraged.

Background: Central nervous system (CNS) tumors are a major and growing global health-care challenge. Western Saudi Arabia has an inconsistent data registry; therefore, the epidemiology of CNS tumors is unclear across the country. This study is aimed to assemble the epidemiological matrices of CNS tumors from the Western Province of Saudi Arabia. Method: A retrospective analysis was performed using clinical data obtained from three neuroscience centers in Western Saudi Arabia in the period 2014-2019. The sample size included 663 adult and pediatric cases from the local and expatriate populations diagnosed with CNS tumors. Distributions of age, gender, clinical presentation, tumor location, type of surgery, histological subtype, genetic identities, and recurrence rate were explored. Results: The analysis included 500 adult cases and 163 pediatric cases up to 18 years of age with a male to female ratio of 1.16. The mean age at diagnosis was 38 years (± 22.6 years).The supratentorium was the most common location (in 515 cases, 77.7%). Most patients presented with headache (n=298, 44.9%) followed by focal neurological deficit (19.9%). The most common primary CNS tumor was glioblastoma (n=234, 35.3%) followed by meningioma (n=100, 15%). Recurrence rate after surgery was estimated to be 40.9% among all CNS tumors. Conclusion:This is the first tumor registry of Western Province of Saudi Arabia that describes the distribution of primary CNS tumors and highlights their epidemiological matrices. Several incidence trends for histological type, age group, sex, location, and recurrence were determined, and some genetic identities were recognized.

Objective To assess the recurrence interval and predictive significance of TP53 expression and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastomas treated with radiotherapy and combined chemotherapies, including temozolomide, lomustine, procarbazine and bevacizumab. Method We reviewed the clinical outcomes of 52 totally resected glioblastoma patients, who received conventional radiotherapy and temozolomide with other chemotherapeutic agents. Correlation of TP53 expression and MGMT promotor methylation with recurrence interval was analyzed using Kaplan Meier estimates. Results No significant association was found between MGMT promotor methylation and TP53 expression in glioblastomas (P-value = 0.158). Patients with non-methylated MGMT who received temozolomide chemotherapy with other chemotherapeutic agents showed significantly later recurrence (P-value = 0.007) compared with patients with non-methylated MGMT who received temozolomide alone. No significant difference was found in recurrence interval among glioblastoma patients with methylated MGMT who received temozolomide alone or with other chemotherapies (P-value = 0.667). Moreover, patients with non-TP53-expressing tumors who received temozolomide with other chemotherapies had significantly later recurrence (P-value = 0.04) compared with patients who received temozolomide alone. Conclusion Totally resected glioblastoma patients, with non-methylated MGMT or non-TP53-expressing tumors treated with radiotherapy and combined chemotherapies had a reduced chance of tumor recurrence and a more favorable outcome. Furthermore, both MGMT and TP53 are independent prognostic factors for glioblastoma.

Objective: Intraoperative frozen section (IOFS) diagnosis of brain tumors plays an important role in assessing the adequacy of the sample and determining the treatment plan. The aim of this study was to investigate the diagnostic accuracy between IOFS and permanent sections. Material and Method:The authors reviewed the histopathological results of 383 brain tumors, including IOFS and permanent histological diagnosis. The cases were classified into three diagnostic compatibilities (i) Perfect fit; the diagnosis of IOFS was identical to the permanent diagnosis, (ii) Partial compatibility; IOFS diagnosis was not incorrect but was too broad to be considered full compatibility, (iii) Conflict; IOFS diagnosis is completely different from the permanent diagnosis. The permanent diagnosis was used as a primary criterion and was compared to IOFS diagnosis and recurrence rate using different statistical methods.Results: 84% of the patients underwent craniotomy and tumor resection, while 15% only underwent tumor biopsy. Approximately, 53.8 % of the cases revealed perfect matching in the diagnosis between IOFSs and permanent sections, while 16.2% of the cases revealed complete mismatching in the diagnosis between the sections. The remaining 30% of the cases showed partial compatibility in the diagnosis between the two diagnostic methods. There was no significant difference in recurrence rate among all cases of different diagnostic compatibility (p=0.54). Conclusion:There is a diagnostic discrepancy between IOFSs and permanent sections. However, cases that revealed no consensus in the diagnoses showed no negative effect on the patient outcome. Further studies should be conducted to explore the reasons of this conflict in the two diagnostic methods.

Wilms tumor 1 (WT1) gene has recently shown a role in gliomagenesis, making it a potential immunotherapy target in glioblastomas. We aimed to investigate the most sensitive method to detect WT1 expression in glioblastoma and explore the relationship between WT1 expression, IDH1 mutation and recurrence interval. Patients and Methods: Clinical data were collected from 44 patients with glioblastomas, treated with adjuvant therapies. WT1 expression was assessed in all cases using immunohistochemistry (IHC), while its gene expression was assessed in 13 clustered samples using polymerase chain reaction (qPCR). IDH1 mutation was assessed using IHC. The sensitivity between IHC and RT-qPCR was examined. Kaplan-Meier curves were used to compare the recurrence-free interval (RFI) between IDH1 and WT1 expression groups. Results: IDH1 wildtype was found in 26 cases (59.1%) and the remaining 18 cases (40.9%) were IDH1 mutant . Through IHC, WT1 was overexpressed in 32 cases (72.7%), partially expressed in 9 cases (20.5%) and not expressed in only 3 cases. For the 13 cases tested by qPCR, 6 cases showed WT1 upregulation and 7 cases showed WT1 downregulation. There was no significant difference in WT1 expression among cases with different RNA concentrations regardless the testing method (p-value >0.05). However, the difference between IHC and qPCR was significant. IDH1 mutant cases with WT1 overexpression showed significant difference in RFI (p-value =0.048). Conclusion:Parallel testing for WT1 expression using IHC and qPCR is not reliable. However, IHC provides more accurate results. Moreover, IDH1 mutant glioblastomas with WT1 overexpression are associated with late RFI particularly if temozolomide with additional chemotherapies are used.

Background The Wilms tumor 1 (WT1) gene has recently been shown to play a role in gliomagenesis, making it a potential immunotherapy target in glioblastomas. We aimed to investigate the most sensitive method to detect WT1 expression in glioblastoma and explore relationship between WT1 expression and isocitrate dehydrogenase-1 (IDH1) mutation. Methods Clinical and biological data were collected from 44 patients with totally resected glioblastomas, treated with adjuvant therapies, in the period between 2015 and 2019. WT1 protein expression was assessed in all cases using IHC while its gene expression was assessed in 13 clustered samples using quantitative polymerase chain reaction (qPCR). IDH1 mutation was assessed using immunohistochemistry (IHC). McNemar test was used to compare the sensitivity between IHC and RT-qPCR for WT1 gene expression detection. Kaplan Meier curves were used to compare the distribution of recurrence-free interval (RFI) between IDH1 and WT1 expression groups. Results The mean age was 54-years, with a male to female ratio 1.45. IDH1-wildtype was found in 26 cases (59.1%) and the remining 18 cases (40.9%) were IDH1-mutant. Through IHC, WT1 was overexpressed in 32 cases (72.7%), partially expressed in 9 cases (20.5%) and not expressed in only three cases (6.8%). For the 13 cases tested by qPCR, 6 cases showed WT1 gene up-regulation and 7 cases showed WT1 down-regulation. There was no significant difference in WT1 expression among cases with different RNA concentrations regardless the testing method (P-value < 0.05). However, the difference between IHC and qPCR revealed 83% sensitivity, 28.5% specificity and 53% accuracy. IDH1-mutant cases with WT1 overexpression showed significant difference in recurrence interval (P-value < 0.048). This significance was not seen among IDH1-mutant cases with WT1 partial or no expression (P-value = 0.56). There was also no significant difference in recurrence interval among IDH1-wildtype cases with WT1 partial or overexpression (P-value = 0.83). Conclusions Parallel testing for WT1 expression using IHC and qPCR is not reliable. However, IHC provides more accurate results than does qPCR, which runs on fragmented tissue with indeterminant RNA concentrations. Moreover, IDH1-mutant glioblastomas with WT1 overexpression are associated with slow recurrence interval particularly if temozolomide with additional chemotherapies are used.