Correlation of immunohistochemical expression of HIF-1alpha and IDH1 with clinicopathological and therapeutic data of moroccan glioblastoma and survival analysis.

INTRODUCTION: Glioblastomas are aggressive primary intracranial tumours of the central nervous system causing significant mortality and morbidity worldwide. OBJECTIVE: This study aims to evaluate the prognostic value of tissue expression by immunostaining of hypoxia-inducible factor (HIF-1α), isocitrate dehydrogenase 1 (IDH1), and tumour protein p53 in glioblastoma in Moroccan patients. The association of HIF-1α, IDH1, and p53 expression with the clinicopathological data and overall patient survival (OS) was also evaluated. MATERIALS AND METHODS: Confirmed glioblastomas were included in this study. Twenty-two tissue samples were obtained by neurosurgical intervention resulting from total resection, and subtotal resection or biopsy. Karnofsky index, histological type of tumour, and the status of IDH1, p53 protein, and HIF-1α expression by immunostaining were reported. RESULTS: The majority of the patients were males (64%) with a sex ratio of 1.75. The average age was 54 ± 13. Median follow-up was 10.10 months and median overall survival was 10 months. The expression of HIF-1α was high in 10 samples (45%) and low in 12 (55%). There was a statistically significant difference in OS of 85% at 12 months for the subgroup of patients "HIF-1α negative IDH1 positive" p = 0.038, the unadjusted analysis showed that the group "HIF-1α positive, IDH1 positive" was a poor prognostic factor, the HR was 0.08 (95% CI: 0.009-0.756, p = 0.027). CONCLUSION: Patients with negative HIF-1α expression and positive IDH1 expression have a better prognosis, suggesting that these two biomarkers may be useful in the search for new approaches for targeted therapy in glioblastoma.

Incidence of neural tube defects and their risk factors within a cohort of Moroccan newborn infants.

BACKGROUND: Neural tube defects (NTDs) are a group of birth defects that result from a partial or complete failure of the neural tube to close during embryogenesis. Their prevalence varies between 0.5 to 2 per 1000 births in countries without folic acid supplementation. The aim of our study is to assess the NTDs incidence and describe the risk factors within Moroccan newborn infants. METHOD: This is a descriptive study over a period of 5 and a half years including all births at "Les Orangers" Maternity and Reproductive Health Hospital of Rabat with notification of NTD cases, whether isolated or combined with other anomalies. Data were reported on pre-established sheets and on the teratovigilance registry. Statistical analysis was performed with SPSS version 18 statistical software. RESULTS: During the study period, 43,923 births were recorded including 44 cases of neural tube defects, an incidence rate of 1 per 1000 births, with a female predominance; sex ratio = 0.8. These defects included anencephaly (50%), spina bifida (38.6%) and encephalocele (11.4%). The risk factors detected during this study include consanguinity (34%), consumption of fenugreek or other plants (36%), diabetes (4.5%) and medication (2.2%). A family history of malformation was reported in 6.8% of cases and among siblings in 4.5% of cases. The average maternal age was 30.38 ± 6.88 and the average gestational age was 36.80 ± 5.11. A quarter of mothers did not benefit from any medical monitoring during pregnancy while 59% did not take folic acid supplementation during the first trimester of pregnancy and none of them took B9 vitamin during the periconceptional period. The antenatal diagnosis was performed in 63% of cases. The mortality rate was 3.8 per 10,000 and 16% of cases evolved positively. CONCLUSION: NTDs require high intensity and multidisciplinary care which stresses the importance, in our context, of strengthening and optimizing acid folic supplementation strategies during the periconceptional period.

Hydroxychloroquine and Azithromycin as a Treatment of COVID-19: Electrocardiogram Variability.

During the COVID-19 pandemic, the effectiveness of the combination of hydroxychloroquine and azithromycin is widely discussed. This treatment can cause many severe cardiac side effects that makes us discuss its utility. The aim of this study is to describe the cardiovascular effect of hydroxychloroquine and azithromycin by analyzing surface ECG in patients with COVID-19. This observational cohort study included Moroccan patients with COVID-19 diagnosis and were hospitalized in Cheikh Khalifa International University Hospital, Casablanca, Morocco between March 26 and April 20, 2020. Patients were treated with a combination of hydroxychloroquine and azithromycin over a period of at least ten days. We were interested in the effects of this combination on the electrocardiogram. A total of 118 eligible patients were enrolled in the study. QT interval prolongation was observed in 19% of patients under the treatment. Only 5 patients required discontinuation of treatment. The factors associated with QT prolongation are male gender (P value 0,043), age over 68 years (P value 0,09), cardiovascular comorbidity (P value 0,013), tisdale score ≥11 (P value < 0,001), and a severe form of COVID-19 (P value < 0,001). First degree atrioventricular block was observed in 2 patients. No serious rhythm or conduction disorders were observed in this study. QT prolongation is a real risk with the combination of hydroxychloroquine and azithromycin. In the current context, it is necessary to select patients at high risk of severe rhythm disturbances that require closer ECG monitoring. Treatment should be discontinued if there are alarming signs such as QTc prolongation beyond 550 ms and the development of ventricular extrasystole or torsade de pointe.

[The inferior laryngeal nerve: anatomical and surgical considerations about 60 thyroidectomy]. / Le nerf laryngé inférieur: considérations anatomiques et chirurgicales à propos de 60 thyroïdectomies.

Thyroid surgery requires a thorough knowledge of cervical anatomy and anatomical variations, in particular of the lower laryngeal nerve, in order to avoid iatrogenic lesions. The objective of our study was to analyze the relationships of the lower laryngeal nerve, the existence of branches of nerve division and a subjective appreciation of the size of the nerve. This is a prospective study of 1 year including 60 patients who underwent thyroidectomy. Sixty patients underwent surgery on the thyroid gland between February 2014 and January 2015 by the same principal operator (10 men and 50 women). The average age of our patients was 51 years. For men were performed 6 total thyroidectomies, 2 left lobo-isthmectomies and 2 right lobo-isthmectomies. For women were performed 33 total thyroidectomies, 8 left lobo-isthmectomies and 9 right lobo-isthmectomies. On the right, the nerve was superficial relative to the artery in 71.6% of cases; it was divided in 33.3% of cases and was abnormally thin in 16.6% of cases. On the left, the nerve was deep in relation to the artery in 83.3% of cases; it was divided in 15% of cases and was abnormally thin in 11.6% of cases. Knowledge of the anatomical variations of the lower laryngeal nerve is essential in thyroid surgery, the risk is particularly important on the right side given the sometimes very small caliber and the existence of branches of division more frequent than on the left side.

Effect of CYP2C9, VKORC1, CYP4F2, and GGCX gene variants and patient characteristics on acenocoumarol maintenance dose: Proposal for a dosing algorithm for Moroccan patients.

We investigated the impact of non-genetics factors, and single nucleotide polymorphisms (SNPs) in VKORC1, CYP2C9, CYP4F2, and GGCX on acenocoumarol dosage in Moroccan adult's patients, in order to develop an algorithm to predict acenocoumarol dose for Moroccan patients. Our study consisted of 217 Moroccan patients taking a maintenance dose of acenocoumarol for various indications. The patients were genotyped for VKORC1 -1639 G>A, VKORC1 1173 C>T, CYP2C9*2, CYP2C9*3, CYP4F2 1347 G>A and GGCX 12970 C>G SNPs. The statistical analysis was performed using the SPSS software. The age and SNPs in VKORC1 and CYP2C9 were significantly associated with the weekly acenocoumarol dose requirement (p = 0.023, p = 0.0001 and p = 0.001 respectively). There was no association found between the weekly acenocoumarol dose and the CYP4F2 or GGCX variants (p-value > 0.05). Non-parametric analysis confirmed the accumulate effect of variant alleles at VKORC1 -1639 G>A, VKORC1 1173 C>T and CYP2C9 SNPs on the acenocoumarol dose requirement. With 90.24% less dose required for one patient carrying homozygote variant at VKORC1 -1173 (TT) and CYP2C9 *x/*x haplotype. The multiple linear regression analysis showed that mutation in VKORC1 -1639, VKORC1 1173 SNPs, or in CYP2C9 haplotype reduces the mean acenocoumarol weekly dose to 25.4%, 23.4% and 6.2%, respectively. The R2 for multiple regression analysis final model was found to be 35.9%. In this work we were able to establish the factors influencing interindividual sensitivity to the anticoagulant therapy that can help physicians to predict optimal dose requirement for long term therapy.

Comparison of SYBR green I real-time RT-PCR with conventional agarose gel-based RT-PCR for the diagnosis of infectious bronchitis virus infection in chickens in Morocco.

BACKGROUND: A rapid, sensitive, and specific molecular method for the diagnosis of infectious bronchitis virus (IBV) infection is important in curbing infectious bronchitis outbreaks in Morocco and other countries. METHODS: In this study, an easy-to-perform SYBR green I real-time reverse transcriptase polymerase chain reaction (RT-PCR) targeting the nucleocapsid gene of IBV was developed and compared with conventional agarose gel-based RT-PCR for the detection of IBV infection. RESULTS: We found that the SYBR green I real-time RT-PCR was at least 10 times more sensitive than the agarose gel electrophoresis detection method. The assay exhibited high specificity for IBV infection. All negative controls, such as Newcastle disease virus, infectious bursal disease virus, and avian influenza virus, were not detected. CONCLUSION: The SYBR green I real-time RT-PCR test described herein can be used to rapidly distinguish IBV from other respiratory pathogens, which is important for diagnosis and control of infectious bronchitis outbreaks in Morocco. The test is a valuable and useful method as a routine assay for diagnosis of clinical IBV infection in commercial chickens.

Prevalence and molecular characterization of avian infectious bronchitis virus in poultry flocks in Morocco from 2010 to 2014 and first detection of Italy 02 in Africa.

The aim of this study was to investigate the prevalence and diversity of infectious bronchitis virus (IBV) genotypes in poultry flocks in 16 areas of Morocco between 2010 and 2014. A total of 360 chicken flocks suspected of being infected by IBV were screened for the IBV N gene using real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Flocks were classified into four groups according to their IBV vaccination programme. Group 1 contained unvaccinated birds. Group 2 received a single application of live H120 vaccine. Groups 3 and 4 birds received one or two booster vaccination(s), respectively, mostly using the H120 vaccine. The real-time RT-PCR results showed that 51.7% of the flocks were positive for the IBV genome with geographical disparities. Molecular characterization of IBV was performed on 50 RT-PCR positive samples by partially sequencing the S1 gene, including the hypervariable regions (nucleotides 705-1097). Two predominant genotypes were detected, with the Massachusetts type dominating (66%), among which 25% of the samples were identical to the H120 vaccine. The second most common genotype (present in 32% of the flocks) was surprisingly Italy 02, revealing the first detection of this genotype in Morocco and also in Africa. 793B, the predominant genotype in the late 1990s in Morocco, was only detected on one occasion and was identical to the 4/91 vaccine strain. This study highlights the high prevalence of IBV in poultry farms in Morocco and confirms its continuous dynamic changes and evolution.