Suicide and depressive symptoms possible correlates among a sample of Egyptian physicians: observational cross-sectional study (online survey).

BACKGROUND: Compared to other occupations, physicians are more susceptible to depression and suicide. Suicide among physicians in some countries reached up to 1.5- to threefold higher than the general population. However, this rate was not homogenous in all countries. Most of the Egyptian studies were related to the stressful pandemic event, but the actual prevalence of depression among physicians is still under research. To the best of the researcher's knowledge, no other study has been conducted to evaluate the risk of suicide among Egyptian physicians. AIM: The study aimed to screen for depressive symptoms and suicide among Egyptian physicians and to investigate the correlates associated with suicide ideations. METHODS: This cross-sectional survey included Egyptian physicians recruited online by Google Forms. Depressive symptoms were screened using the Beck Depression Scale (BDI-II), while suicidal ideas were assessed using the Suicidal Ideation Attributes Scale (SIDAS). RESULTS: Six hundred sixty Egyptian physicians completed the survey following a two-week pilot study between January 10 and July 16, 2023. The average age was 39.1 years, and 71.4% were married. 49.1% were medical specialists. The median daily working hours were eight, and 27.7% of the physicians attended night shifts. 22.3% had a psychiatric illness, and 34.3% had a chronic disease. Younger and single physicians of both sexes were more prone to suicide risk (p-value = 0.019 and 0.021, respectively). Those with psychiatric or chronic medical disorders had a higher suicidal risk (p-values < 0.001 and 0.004, respectively). Physicians with fewer academic degrees and those who work longer hours or night shifts had more depressive symptoms (p-values < 0.001 and 0.009, respectively). The risk of depression and suicide is almost the same in all medical specialties. The SIDAS suicide score and the Beck depression score revealed a statistically significant association (r = 0.288, p-value < 0.001). CONCLUSION: Suicide risk is higher among younger, single physicians of both sexes, as well as those with psychiatric or chronic medical disorders. More depressive symptoms are seen in physicians who have more extended hours or night shifts and who have fewer academic degrees. Almost all medical specialties carry the same risk of depression and suicide. Longitudinal research is recommended for regular follow-up of suicidal thoughts and depressive symptoms.

Effect of health belief model-based educational intervention on prostate cancer prevention; knowledge, practices, and intentions.

BACKGROUND: Prostate cancer screening is a crucial preventive element for improving the survival rates of prostate cancer. Therefore, our research objective was to investigate the effect of health belief model-based education on prostate cancer knowledge, health beliefs, and preventive health practices among adult and older adult males. METHODS: A one-group pre-test/post-test quasi-experimental study design was carried out at the one-day outpatient clinics affiliated to General Alexandria Main University Hospital. We enrolled 110 men aged 45-75 years old in a health belief model-based educational intervention program. Various questionnaires were utilized to gather data before, immediately after, and three months following the intervention. These questionnaires included the socio-demographic questionnaire, Prostate Cancer Knowledge Questionnaire (PCKQ), Prostate Cancer Screening-Health Belief Model Scale (HBM-PCS), Prostate Cancer Preventive Practices Questionnaire (PCPPQ), and one question regarding the intention to undergo PC screening. RESULTS: Participants' knowledge about prostate cancer screening improved significantly immediately after the program and this positive change was maintained at the follow-up (p = 0.000). Furthermore, participants' perceptions and preventive practices towards prostate cancer screening had changed significantly after program completion and at follow-up (p = 0.000). After program completion, many of the participants (92.7%) expressed their intention to undergo prostate cancer screening within the coming six months (p = 0.000). The younger age group (45-49 years) showed higher scores in their perception of prostate screening (p = 0.001). Higher education and income were significantly associated with higher scores in the three scales (p = 0.000 in all scales). CONCLUSION: The study findings emphasized the effectiveness of the designed health educational program based on the HBM on PC preventive behaviors, through significantly improving participants' knowledge level, perceptions, practices, and intentions to PC screening. The program is highly recommended for prostate cancer preventive health practices among both adult and older adult males.

Genetic Polymorphism Study of IDH 1/2 and TET2 Genes in Acute Myeloid leukemia Patients.

BACKGROUND AND OBJECTIVE: Isocitrate dehydrogenase genes (IDH1 and IDH2) encode important enzymes that play pivotal role in cellular metabolism. Mutations in TET2 have been demonstrated to contribute to DNA hypermethylation, either expression of mutant IDH1/2 or TET2 resulted in poor cell differentiation and epigenetic alterations in hematopoietic cells, suggesting a sharing of the oncogenetic impact. In this study, we investigated the frequency of genetic alterations in IDH1/2 and TET2 genes in Egyptian cohort of adult patients with de novo AML, and the association of IDH1/2 and TET2 genetic Polymorphism with AML prognostic criteria and explore prognostic molecular markers with clinical outcome. METHODS: The SNP assay for IDH1, IDH2 and TET2 genes polymorphism tested with RT-PCR included three polymorphisms that are rs121913500, rs121913503, and rs2454206 respectively, were tested on 141 adult Egyptian patients fulfilling the AML diagnostic criteria. RESULT: The incidence of IDH mutations is 11/141 (7.8%); 5/141 (3.5%) IDH1 mutant and 6/141 (4.3%) IDH2 mutant. And the incidence of TET2 mutations is 72/141 (51.1%); 15/141 (10.7%) homozygous mutation and 57/141 (40.4%) heterozygous mutations. IDH1, IDH2 and TET2 genes mutations with DFS and OS in AML patients were not significantly correlated. CONCLUSIONS: TET2 SNP is common in Egyptian AML patients. Further research on IDH, TET2 and their relationships to other hematological malignancies and leukemogenesis transformation is advised and a study of a larger number of cases is needed for potential statistical significance.

A Study to Explore the Role of IDH1 (R132) Mutation on Imatinib Toxicity and Effect of ABCG2/OCT1 Expression on N-Desmethyl Imatinib Plasma Level in Egyptian Chronic Myeloid Leukemia Patients.

Imatinib mesylate (IM) is the gold standard for treatment of Chronic Myeloid Leukemia (CML). This study aimed to gain more knowledge of the altered PK, pharmacogenetic factors, and gene expression leading to variable IM levels. Fifty patients with chronic phase-CML were enrolled in this study and divided as 25 responders and 25 non-responders (patients are directly recruited after response assessment). HPLC/MS/MS was used to determine trough and peak concentration of imatinib and N-desmethyl imatinib in the blood. PCR-RFLP technique was used to detect IDH1 gene mutation (R132). The median value of IM trough level was significantly higher, the P/T ratio was significantly lower and the α-1-acid glycoprotein (AGP) was significantly higher among responders compared to non-responders (P=0.007, 0.009 and 0.048, respectively). Higher N-desmethyl imatinib peak plasma concentration was observed with low mRNA expression of ABCG2 and OCT1 (P=0.01 and 0.037, respectively). IDH1 R132 gene mutation was associated with a significant increase in toxicities (P=0.028). In conclusion, IM trough level, P/T ratio and AGP was significantly higher in responders. In addition, ABCG2 and OCT1 gene expression may affect the interindividual PK variation. Although a prospective study with a larger patient population is necessary to validate these findings. IDH1 mutation is a predictor of increased toxicity with IM treatment.

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.

Assessment of apheresis platelets during 5 days of storage: A National Cancer Institute, Cairo University experience.

BACKGROUND: Platelet transfusion therapy is widely used to prevent hemorrhage in patients with thrombocytopenia and platelet disorders. The platelet concentrate (PC) quality is affected by increased storage time, as reflected in the decreased number of platelets, morphological changes, and impaired functions. This study aimed to analyze the impact of 5 days storage on platelets count and the expression of CD63, and Annexin V as activation markers during PC storage. METHODS: Fifty PCs collected from single donors were tested for platelet count on days 0, 3, and 5 using a Sysmex blood counter. CD61, CD63, and Annexin V expression was analyzed by a multicolor Navios flow cytometer. RESULTS: There was a significant decrease in platelet count during 5 days of storage. There was a direct relationship between storage time and degree of platelet activation. CD63 had almost double increased expression on day 5 than day 3. Annexin V showed significantly increased expression on day 3 with minor differences between days 3 and 5. CONCLUSION: According to standard blood bank conditions, PC stored for 5 days showed a degree of in vitro activation as evidenced by CD63 and Annexin V expression, may lead to reduced therapeutic efficacy. Flow cytometry monitoring platelet activation in PC offers a better understanding of the changes during PC storage and may help improve platelet products.

Regulation of CDK inhibitor p27 by microRNA 222 in breast cancer patients.

BACKGROUND: Breast cancer is the most common of all cancers and the second leading cause of cancer-related deaths among women worldwide. MicroRNAs regulate at least 60% of the human genes, including tumor suppressor genes and oncogenes, and can thereby affect cancer risk. In this study, the prognostic values of the CDK inhibitor p27 and miR-222 as biomarkers for breast cancer were evaluated. METHODS: The real-time quantitative polymerase chain reaction method was employed to measure the expression level of miR-222, whereas the serum levels of the CDK inhibitor p27 were measured via enzyme-linked immunosorbent assay. The levels were determined in sera from 110 participants representing three different groups. RESULTS: Patients with breast cancer exhibited significantly higher expression levels of miR-222 and lower levels of CDK inhibitor p27 than the control group. In addition, a statistically significant inverse correlation between miR-222 and the CDK inhibitor p27 was observed. The receiver operating characteristic curves plotted for serum p27 and miR-222 helped in significantly differentiating between breast cancer patients and controls but could not discriminate between those with stage II and stage III cancer. CONCLUSION: Thus, a significant upregulation in the serum miR-222 levels was observed in cancer patients, and a significant inverse correlation was noted between the miR-222 and CDK inhibitor p27 expression levels. These findings indicate that miR-222 may be used as a useful noninvasive screening biomarker for human breast cancer. MICROABSTRACT: Novel biomarkers for prognosis, prediction, and therapeutic purposes are essential as the prognosis and therapeutic targets of breast cancer are dependent on traditional markers, such as the tumor stage and hormonal receptor status. This study aimed to evaluate the diagnostic and prognostic values of the CDK inhibitor p27 and miR-222 in breast cancer. Our results indicated that miR-222 and the CDK inhibitor p27 may be used as noninvasive biomarkers to screen for human breast cancer but cannot discriminate between patients with early breast cancer and patients with advanced breast cancer.

FLT3-ITD Allele Frequency Is an Independent Prognostic Factor for Poor Outcome in FLT3-ITD-Positive AML Patients.

BACKGROUND: FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) is a molecular genetic alteration significantly affecting the clinical outcome in patients with acute myeloid leukemia (AML). FLT3-ITD mutations are characterized by variable mutant-to-wild allelic ratios (ARs) and sizes of the duplicated sequences. The size of the inserted sequence may vary from a few to hundreds of nucleotides. The aim of this work was to determine the impact of FLT3-ITD ARs, FLT3-ITD allelic frequency (AF), and allele size in de novo AML. PATIENTS AND METHODS: We studied 117 patients with FLT3-ITD gene mutation-positive AML, dividing them into those with low ARs and those with high ARs (>0.64) and examined their prognostic impact. RESULTS: High FLT3-ITD AR ≥ 0.64 and AF ≥ 0.5 were significantly associated with a lower overall survival compared with lower AR (median 0.625 vs. 1.020 months, respectively; P = .041) and AF (median 0.493 vs. 0.954 months, respectively; P = .009). NPM1 mutation had no favorable impact on the low-level FLT3-ITD group. CONCLUSION: Initial high total leukocyte count, FLT3-ITD AF, and splenomegaly are independent prognostic factors for poor outcome in FLT3-ITD-positive AML.

Relation between GSTP1 polymorphism and oxidative stress in patients with hepatocellular carcinoma.

BACKGROUND: Glutathione can reduce the oxidative stress by converting the unstable to stable molecules and its status in hepatocellular carcinoma (HCC) is correlated with tumor growth and metastasis. Glutathione S-transferase Pi (GSTP1) is reported to detoxify the xenobiotic substrates by catalyzing their conjugation to reduced glutathione (GSH) and its over-expression was demonstrated in the early stages of HCC, while loss of GSTP1 has been suggested to increase the risk of deoxyribonucleic acid (DNA) damage and mutation. The aim of this study is to assess the relationship of GSTP1 polymorphism Ile105Val (rs1695 A > G) with HCC risk, and to investigate the oxidative stress status of HCC patients by measuring the antioxidant glutathione (GSH) levels. This study was conducted on 99 newly diagnosed HCC patients and 80 apparently healthy individuals as a normal control group. All participants were subjected to the measurement of plasma GSH levels according to Ellman's method, and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the detection of GSTP1 polymorphismIle105Val (rs1695 A > G). RESULTS: The occurrence of either the mutant homozygous or the mutant heterozygous genotype of GSTP1 was significantly higher in HCC patients, while the occurrence of the wild genotype was significantly higher among the normal control subjects. Mutant GSTP1 genotype, older age, male gender, and high serum alanine aminotransferase (ALT) were associated with increased risk of development of HCC. The best sensitivity, specificity, PPV (positive predictive value), NPV (negative predictive value), and overall diagnostic performance for plasma GSH at a cutoff level of 2003.5 µM/mg were 57.6%, 52.5%, 60%, and 40%. The area under the curve for GSH was 0.562. CONCLUSION: Mutant GSTP1 genotype was an independent prognostic factor for increased HCC risk which can be used in a risk assessment model for HCC. Plasma GSH presents insufficient sensitivity and specificity for HCC.

Frequency and specificity of Red blood cell alloantibodies in multitransfused Egyptian patients with hematological and nonhematological malignancies.

BACKGROUND: Repeated blood transfusions can result in the production of alloantibodies against one or more red blood cell (RBC) antigens, which can complicate future transfusions. AIM: This study aims to determine the frequency and specificities of RBC alloantibodies in multitransfused adult cancer patients admitted at the National Cancer Institute, Cairo University. METHODS: This cohort study enrolled 2000 multitransfused cancer patients diagnosed with different types of malignancies; they were screened for RBC alloantibodies using Serascan Diana 3 and Identisera Diana 11-cell identification panels (Diagnostic Grifols, Spain). RESULTS: Of the 2000 patients tested, 25 had autoantibodies and were excluded from the study. Of the remaining 1975 patients, 181 patients had a total of 267 different alloantibodies (9.16%), with some having more than 1 antibody detected. Our study showed that more female patients (63%) than male patients (37%) had acquired RBC alloantibodies, and a higher prevalence of alloantibodies in patients with nonhematological malignancies (14%) compared with those with hematological malignancies (6.5%). The highest percentage of alloantibodies belongs to the Rh blood group system, followed by the Kell system, then Duffy, MNS, Kidd, and Lewis. Patients who received combined chemotherapy and immunotherapy exhibited a lesser antibody response compared to other patients. CONCLUSION: The prevalence of alloimmunization in our study is comparable to previous reports on oncology patients. Repeated blood transfusions, which can lead to alloimmunization, often complicate future transfusions. Therefore, we recommend extending phenotype matching for patients who are presumed to depend on blood transfusions in the long term.

Impact of Lymph Node Sampling in Stage II and III Epithelial Ovarian Cancer Patients with Clinically Negative Lymph Nodes.

The main surgical treatment of stage II and III epithelial ovarian cancer (EOC) is complete cytoreduction, while the main role of lymph node sampling is to exclude microscopic stage III disease in an apparent stage I EOC. This study aims to evaluate the impact of lymph node sampling in stage II and III EOC patients with clinically negative lymph nodes. This is a retrospective cohort study including 51 stage II and III EOC patients treated and followed up between 2012 and 2016. They were treated by complete cytoreduction. Sixteen cases had lymph node sampling, while it was not done in 35 cases. The study was performed at National Cancer Institute (NCI)-Cairo University. There was no statistically significant difference regarding overall survival (P value 0.649) or disease-free survival (P value 0.372) between the group of patients who had lymph node sampling and the other group of patients who had no lymph node sampling. Lymph node ratio (LNR) was not associated with a statistically significant impact regarding overall survival or disease-free survival. There is no impact of lymph node sampling on stage II and III EOC patients with clinically negative lymph nodes.

Hyperthermic Intraperitoneal Chemotherapy as a Treatment for Epithelial Ovarian Cancer.

Treatment by cytoreductive surgery (CRS) and intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) has been an option for selected patients with peritoneal carcinomatosis. This study aims to evaluate the impact of HIPEC in epithelial ovarian cancer (EOC). A retrospective observational cohort study including 48 EOC patients treated and followed up between 2012 and 2016. Thirty-seven cases were treated by CRS only, while 11 cases were treated by CRS and HIPEC. The study was performed at National Cancer Institute (NCI)-Cairo University. There was no statistically significant difference regarding overall survival or disease-free survival between the group of EOC patients treated by CRS only and the one treated by CRS and HIPEC. Presence of ascites and histological types (serous/non-serous) were the significant independent variables related to overall survival. Presence of ascites was the only independent variable associated with a significant relation to disease-free survival. No statistically significant impact of HIPEC in treatment of EOC was found in this study.

Low Expression and Promoter Hypermethylation of the Tumour Suppressor SLIT2, are Associated with Adverse Patient Outcomes in Diffuse Large B Cell Lymphoma.

SLIT2 has been classified as a major tumour suppressor gene due to its frequent inactivation in different cancer types. However, alterations of SLIT2 expression and relation to patient outcomes in diffuse large B cell lymphoma (DLBCL) remain undefined. The aim of this study was to investigate the expression and the methylation status of SLIT2 gene as well as its relation to patient outcomes in DLBCL. Immunohistochemical (IHC) staining was carried out to detect the expression of SLIT2 in a series of 108 DLBCL cases. Re-analysis of previously published dataset (GSE10846) that measured gene expression in DLBCL patients who had received CHOP or R-CHOP therapy was performed to identify associations between SLIT2 and patients survival. Laser capture microdissection was performed to isolate GC B cells and DLBCL primary tumor cells. Bisulfite treatment and methylation-specific PCR (MSP) analysis were done to assess SLIT2 promotor methylation status. We report that the expression of SLIT2 protein was reduced in a subset of DLBCL cases and this was significantly correlated with advanced clinical stage (p = 0.041) and was an independent predictor of worse overall survival (OS) (p = 0.012). Re-analysis of published gene expression data showed that reduced SLIT2 mRNA expression was significantly correlated with worse OS in R-CHOP-treated ABC DLBCL patients (p = <0.01). Hypermethylation of the SLIT2 promotor was significantly correlated with low SLIT2 expression (p = 0.009). Our results provide a novel evidence of reduced expression of SLIT2 that is associated with promoter hypermethylation and adverse outcomes in patients with DLBCL.

Topoisomerase II α Gene alteration in Triple Negative Breast Cancer and Its Predictive Role for Anthracycline-Based Chemotherapy (Egyptian NCI Patients)

Objective: Triple negative breast cancer is an aggressive variant of breast cancer; it forms about 15% of breast cancer cases. It lacks the responsiveness to hormonal and targeted therapies. Anthracyclines remain the treatment option for these patients. Anthracyclines are cardiotoxic, so predicting sensitivity of response by biological predictors may have a role in selecting suitable candidates for these drugs. Material and methods: This study included 50 TNBC cases, from National Cancer Institute, Cairo University(NCI-CU), Egypt, who underwent surgery and received adjuvant chemotherapy. Archived blocks were obtained and immunostaining for Ki-67 LI and Fluorescent In situ Hybridization (FISH) technique to assess TOP2A gene copy number and chromosome 17CEP status were done. Analysis of association between TOP2A alterations and CEP17 polysomy as well as Ki-67 LI with other clinicopathological parameters was done. Associations between the biological markers and event free survival (EFS) and overall survival (OS), were also performed. Results: TOP2A alteration was seen in 9/50 cases (5 amplified and 4 deleted). CEP17 Polysomy was detected in 14% of cases. Most of patients (80%) showed Ki-67 LI ≥20%. There was a significant association between TOP2A gene and CEP17 status. Outcome was better with abnormal TOP2A gene status and CEP17 polysomy, radiotherapy and combined anthracyclines and taxanes in the adjuvant setting, however P-values were not significant. Conclusion: TOP2A gene alterations and CEP17 polysomy may have prognostic and predictive role in TNBC treated with adjuvant Anthracyclines.

Combined cytoreductive surgery and hyperthermic intraperitoneal chemotherapy as a treatment for recurrent epithelial ovarian cancer-National Cancer Institute experience.

BACKGROUND: Complete cytoreduction has been associated with survival benefit in the treatment of recurrent epithelial ovarian cancer (EOC). In this study, the aim is to investigate the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of recurrent EOC. PATIENTS AND METHODS: This is a descriptive (case series) study including 9 patients with recurrent EOC treated by CRS and HIPEC. They were treated and followed up between December 2011 and December 2017. The study was performed at The National Cancer Institute (NCI) - Cairo University (CU). RESULTS: Postoperative death occurred in 2 cases, while recurrence occurred in one case. Six cases had smooth postoperative course and free follow-up. Median follow-up period was 39 months, ranging from 29 to 47 months. Median overall survival was 42 months while median disease-free survival was not reached. CONCLUSIONS: Treatment of recurrent EOC by CRS and HIPEC appears to be promising. However, this line of treatment requires further evaluations and larger studies for better assessment of the potential survival benefits and possible complications.