Prognostic value of RGS1 and mTOR Immunohistochemical expression in Egyptian multiple myeloma patients; A single center study.

INTRODUCTION: Prognostic factors in plasma cell myeloma were proved to be related to signaling pathways and associated transcription factors. RGS1 and mTOR were known to play an important role in the pathogenesis of multiple myeloma. The aim of the study was to evaluate the expression and the prognostic value of RGS1 and mTOR and their relation to clinical as well as other diagnostic criteria in multiple myeloma. PATIENTS AND METHODS: The present study included 44 denovo Myeloma patients, recruited from the Medical Oncology Department, National Cancer Institute, Cairo University. Detection of RGS1 and mTOR expression was performed using Immunohistochemical staining on bone marrow biopsy sections. RESULTS: The median age was 51 years with male to female ratio 1.58:1. There was a positive highly statistically significant correlation between RGS1 and mTOR among all studied cases (p value <0.001). Regarding their prognostic value, there was a highly statistically significant association of the expression levels of RGS1 and mTOR with treatment response (p <0.001). Finally, there was a significant influence of RGS1 and mTOR on overall survival probability (p value <0.001 and <0.002 respectively) with better survival for those having low expression. CONCLUSION: RGS1 and mTOR were suggested as poor prognostic markers in MM patients, being associated with lower response rate and inferior OS. We recommend considering RGS1 and mTOR as one of the prognostic criteria in different risk stratification and staging classifications. Further trials for RGS1 and mTOR targeting in multiple myeloma are recommended.

Laboratory biomarker predictors for disease progression and outcome among Egyptian COVID-19 patients.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic resulted in more than five hundred million infected cases worldwide. The current study aimed to screen the correlation of different laboratory findings with disease severity and clinical outcomes of coronavirus disease (COVID-19) among Egyptian patients to obtain prognostic indicators of disease severity and outcome.A total of 112 laboratory-confirmed COVID-19 patients were examined. According to the severity of the disease, these patients were divided into three main groups: mild, moderate and severe cases. In addition, clinical characteristics and laboratory findings, including Hb, platelet count, white blood cell count, lymphocyte percentage, neutrophil percentage, neutrophil lymphocyte ratio (NLR), D-dimer, highly sensitive C-reactive protein (HS-CRP), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and creatinine, were measured.The presence of hypertension and/or diabetes was found to be a significant risk factor for disease severity and poor outcome. Increased respiratory rate, levels of SpO2, HS-CRP, D-dimer, NLR, ALT, LDH, lymphopenia and neutrophilia, as well as changes in chest computed tomography (CT), were associated with increased disease severity and fatal consequences. Highly sensitive C-reactive protein, D-dimer, NLR and LDH constituted excellent predictors for both disease severity and death.Laboratory biomarkers, such as HS-CRP, D-dimer, NLR and LDH, are excellent predictors for both disease severity and death. They can predict mortality in patients at the time of admission secondary to SARS-CoV-2 infection and can help physicians identify high-risk patients before clinical deterioration.

Detection of exosomal miR-18a and miR-222 levels in Egyptian patients with hepatic cirrhosis and hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is known to be the second leading cause of cancer-related mortality worldwide. For improving the prognosis as well as reducing the rate of mortality, early diagnosis of HCC is a must. AIMS: This study was conducted to assess the ability of the serum expression of exosomal miR-18a and miR-222 to differentiate and diagnose patients with HCC, patients with liver cirrhosis, and healthy controls. METHODS: This study included 51 patients with liver cirrhosis, 51 patients with HCC on top of hepatitis C virus (HCV) infection, and 50 healthy controls. RESULTS: miR-18a and miR-222 were assessed using reverse transcription-polymerase chain reaction. MiR-18a and miR-222 levels were significantly higher in the liver cirrhosis and HCC groups than the control group (p ˂ 0.001). However, no statistically significant difference was found between patients with HCC and liver cirrhosis (p = 0.4 for miR-18a and p = 0.1 for miR-222). ROC curve analyses to evaluate the diagnostic performances of the two miRNAs as important noninvasive diagnostic markers revealed a best cutoff value of 2 for miR-18a to differentiate between liver cirrhosis, HCC, and healthy controls. And for mir-222, a cutoff value of 1.7 and 1.9 showed the highest specificity for discrimination between liver cirrhosis, HCC, and healthy controls, respectively. Moreover, logistic regression model revealed that miR-18a expression was independent predictive factor in HCC patients (p = 0.004), while miR-222 expression was independent predictive factor in liver cirrhosis patients (p < 0.001). CONCLUSION: miR-18a and miR-222 were significantly discriminative markers between patients with liver cirrhosis and HCC and healthy individuals. Therefore, they have a prognostic rather than a diagnostic value. Moreover, miR-18a and miR-222 could be useful in identifying liver injuries, including fibrosis and cirrhosis.

The Prognostic Significance of c-KIT Mutations in Core Binding Factor Acute Myeloid Leukemia.

BACKGROUND: Many recurrent mutations are encountered in core binding factor acute myeloid leukemia (CBF-AML) which may affect the prognosis. Approximately 20 to 45% of CBF-AML patients have KIT mutations which are having poor prognosis and high incidence of relapse. There is still insufficient data to categorize the patients with c-kit mutation into which risk group and there is a debate around whether Tyrosine kinase inhibitors can decrease the relapse risk and improve the prognosis of those patients. PATIENTS AND METHODS: This study was conducted throughout a period of 3 years, where 102 CBF-AML were enrolled in our study. We analyzed the incidence of c-KIT exon 8 and 17 D816V mutations in CBF-AML patients and studied the prognosis. RESULTS: The prevalence of CBF-AML was 102 of 989 (10.3%), 13.7% and 8.7% in pediatrics and adults' groups respectively. c-KIT fragment mutation analysis revealed a mutant form in 27 of 102 (26.5%) patients. Exon 8 mutation was found in 4 of 40 pediatric and 2 of 62 adult patients, while exon 17 mutation was found in 9 of 40 pediatric and 12 of 62 adult patients. The c-KIT mutations was more common in t(8;21). There was no significant relationship between c-kit mutation and CR rates, while there was a significant inferior overall, disease free as well as progression free survival in the c-KIT mutant patients as compared to the wild group (P value .045, .036 and .024 respectively) in the pediatric group, however, this significance was not evident in the adults' group. CONCLUSION: According to our study, the results may suggest c-KIT mutation as a poor risk factor in pediatric CBF-AML.

Evaluation of MLPA as a comprehensive molecular cytogenetic tool to detect cytogenetic markers of chronic lymphocytic leukemia in Egyptian patients.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia. This disease is genetically heterogeneous, and approximately 85% of patients with CLL harbor chromosomal aberrations that are considered effective prognostic biomarkers. The most frequent aberrations include deletions in 13q14, followed by trisomy 12, and deletions in 11q22.3 and 17p13 (TP53). Currently, fluorescence in situ hybridization (FISH) is the most widely used molecular cytogenetic technique to detect these aberrations. However, FISH is laborious, time-consuming, expensive, and has a low throughput. In contrast, multiplex ligation-dependent probe amplification (MLPA) is a reliable, cost-effective, and relatively rapid technique that can be used as a first-line screening tool and complement with FISH analysis. This study aimed to evaluate the contributions of MLPA as a routine standalone screening platform for recurrent chromosomal aberrations in CLL in comparison to other procedures. Thirty patients with CLL were screened for the most common genomic aberrations using MLPA with SALSA MLPA probemix P038-B1 CLL and FISH. RESULTS: In 24 of the 30 cases (80%), the MLPA and FISH results were concordant. Discordant results were attributed to a low percentage of mosaicism. Moreover, the MLPA probemix contains probes that target other genomic areas known to be linked to CLL in addition to those targeting common recurrent CLL aberrations. CONCLUSIONS: The usage of MLPA as the first screening platform followed by FISH technique for only the negative cases is the most appropriate approach for CLL diagnosis and prognosis.

Genomic characterization of SARS-CoV-2 in Egypt.

Introduction: The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread throughout the globe, causing a pandemic. In Egypt over 115,000 individuals were infected so far. Objective: In the present study, the objective is to perform a complete genome sequence of SAR-CoV2 isolated from Egyptian coronavirus disease (COVID-19) patients. Methods: Nasopharyngeal swabs were collected from 61 COVID-19 patients who attended at National Cancer Institute, Kasr Al-Aini Hospital and the army hospital. Viral RNA was extracted and whole genomic sequencing was conducted using Next Generation Sequencing. Results: In all cases, the sequenced virus has at least 99% identity to the reference Wuhan 1. The sequence analysis showed 204 distinct genome variations including 114 missense mutations, 72 synonymous mutations, 1 disruptive in-frame deletion, 7 downstream gene mutations, 6 upstream gene mutations, 3 frame-shift deletions, and 1 in-frame deletion. The most dominant clades were G/GH/GR/O and the dominant type is B. Conclusion: The whole genomic sequence of SARS-CoV2 showed 204 variations in the genomes of the Egyptian isolates, where the Asp614Gly (D614G) substitution is the most common among the samples (60/61). So far, there were no strikingly variations specific to the Egyptian population, at least for this set of samples.

Covid-19: Urgent Call to Action.

Novel Corona Virus 2019 (COVID-19) is a new virus spread rapidly all over the world. It has specific respiratory or gastrointestinal tract symptoms. Its reported complications include respiratory distress, systemic inflammatory response syndrome, and septic shock. Due to heavy cytokines released by the virus; corticosteroids (40-120 mg / day) were given to severe cases to reduce pneumonia. It's a difficult task to control the spread of SARS-CoV-2, and to invent proper vaccines and treatments. In this review, the existing understanding of fatal, pandemic human coronavirus SARS-Cov2 (COVID-19), with special reference to its diagnosis, origin, transmission, and different approaches to develop its therapeutics, will be discussed.

Significance of CD99 expression in T-lineage acute lymphoblastic leukemia.

BACKGROUND: CD99 was first isolated as an antigen on the T acute lymphoblastic leukemia cells. It has been shown to participate in T cell adhesion and is widely expressed on a variety of hematopoietic and non-hematopoietic cell types. AIM OF WORK: Detection of the expression pattern of CD99 on leukemic and normal T cells and assessing the possibility of its use as a tool for the diagnosis and monitoring of T-ALL cases. METHODOLOGY: We used flow cytometry technique to determine the expression level of CD99 in 62 newly diagnosed T-ALL patients. Patients were followed up for the presence of minimal residual disease on day 15 and day 42 post-therapy. 20 age and sex matched healthy controls were enrolled in our study. RESULTS: CD99 was expressed in all T-ALL patients, with a higher median expression level when compared to controls (58.5% versus 1.38%, p< 0.001). On day 42 post-therapy, 100% of follow up patients who had initial CD99 expression ≤ 50% had no minimal residual disease, while only 45.5% of those who had initial CD99 expression > 50% had no minimal residual disease (P= 0.03). There was no significant influence of CD99 expression on the 1-year overall survival probability (P= 0.82). CONCLUSION: CD99 could be used to complement current strategy relying on TdT for diagnosis and monitoring of minimal residual disease during the post-therapy follow up of T-ALL patients. Further studies are needed to confirm these findings.