Bacterial co-infections in cancer patients with COVID-19: predictors and antimicrobial resistance trends.

INTRODUCTION: Within the context of the coronavirus disease 2019 (COVID-19) pandemic, this study investigated the multifaceted challenges of bacterial infections in cancer patients with COVID-19. It focuses on clinical predictors, resistance patterns, and microbiological characteristics. METHODOLOGY: Over 18 months, 112 adult cancer patients with coronavirus infection confirmed by reverse transcription polymerase chain reaction (RT-PCR) were enrolled. Bloodstream and respiratory samples were evaluated for bacterial infection using the Phoenix automation system for definitive species identification. In vitro susceptibility testing followed the Clinical Laboratory Standards Institute (CLSI) M100-Ed30 guidelines. RESULTS: Bacterial infections affected 25.0% of patients, encompassing bacteremia (21.4%) and respiratory tract infections (8.0%). Multivariable analysis identified hypertension, age < 60, and critical COVID-19 as significant predictors for bacterial infections (p-values = 0.024, 0.029, and 0.039, respectively). Most patients received antimicrobial therapy (93.8%), including last-resort carbapenems (52.7%) and colistin (8.9%). Thirty-three bacterial isolates were identified, with secondary infections doubling co-infection rates. Escherichia coli, Klebsiella species, and Staphylococcus aureus were the most common co-infecting species, while Klebsiella, Acinetobacter, and Pseudomonas species were more frequently associated with secondary infections. Alarmingly, 84.8% of isolates displayed high resistance patterns. All isolated S. aureus species were methicillin-resistant, and 62.5% of Gram-negative bacteria were exclusively sensitive to colistin. CONCLUSIONS: The dominance of highly transmissible hospital-acquired bacterial species, with increased resistance and extensive antibiotic use in COVID-19 patients, necessitates strict infection control and antimicrobial stewardship. Developing customized antimicrobial strategies for cancer patients with COVID-19 is crucial to managing bacterial infections effectively and improving patient outcomes.

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.

Lymphocyte to monocyte ratio predicts survival and is epigenetically linked to miR-222-3p and miR-26b-5p in diffuse large B cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. 10-20% of the patients present with bone marrow (BM) involvement which predicts a worse survival. This study aimed to determine the prognostic significance of serum miR-222-3p, miR-26b-5p, EBV-miR-BHRF1-2-5p, and EBV-miR-BHRF1-2-3p and correlate their levels to clinical and haematological markers in DLBCL with special emphasis on the lymphocyte-monocyte ratio (LMR) and neutrophil-monocyte ratio. We also studied the role of BM BMI1 and PIM2 proteins in predicting BM infiltration. Serum miRNAs were studied on 40 DLBCL and 18 normal individuals using qRT-PCR. BMI1 and PIM2 proteins were studied on BM biopsies by immunohistochemistry. The results were correlated with clinical and follow-up data. All the studied miRNAs were dysregulated in DLBCL serum samples. BMI1 and PIM2 were expressed in 67% and 77.5% of BM samples, respectively. LMR was significantly associated with disease-free survival (DFS) (P = 0.022), miR-222-3P (P = 0.043), and miR-26b-5p (P = 0.043). EBV-miR-BHRF1-2-3p was significantly correlated to haemoglobin level (P = 0.027). MiR-222-3p, miR-26b-5p, and EBV-miR-BHRF1-2-5p expressions were significantly correlated to each other (P = 0.001). There was no significant correlation between the studied markers and follow-up data. LMR is a simple method for predicting survival in DLBCL. MiR-222-3p and miR-26b-5p may be implicated in an immunological mechanism affecting patients' immunity and accordingly influence LMR. The correlation between miR-222-3p, miR-26b-5p, and EBV-miR-BHRF1-2-5p may indicate a common mechanism among the 3 miRNAs that may explain DLBCL pathogenesis.

The Role of Lymphocyte Subsets, PD-1, and FAS (CD95) in COVID-19 Cancer Patients.

Lymphocytes are the main orchestrators that regulate the immune response in SARS-COV-2 infection. The exhaustion of T lymphocytes is a contributing factor to lymphopenia, which is responsible for the COVID-19 adverse outcome. However, it is still not demonstrated on a large scale, including cancer patients. Peripheral blood samples were obtained from 83 SARS-CoV2 infected cancer patients, and 29 COVID-19 infected noncancer patients compared to 28 age-matched healthy controls. Lymphocyte subsets were assessed for CD3, CD4, CD8, CD56, PD-1, and CD95 using flow cytometry. The data were correlated to the patients' clinical features, COVID-19 severity and outcomes. Lymphopenia, and decreased CD4+ T cells and CD8+ T cells were significantly observed in COVID-19 cancer and noncancer patients compared to the control group (p < 0.001, for all). There was a significantly increased expression of CD95 and PD-1 on the NK cells, CD4+ T cells, and CD8+ T cells in COVID-19 cancer and noncancer patients in comparison to the control group. The increased expression of CD95 on CD8+ T cells, as well as the increased expression of PD-1 on CD8+ T cells and NK cells are significantly associated with the severity of COVID-19 infection in cancer patients. The increased expression of CD95 and PD-1 on the CD4+ T cells, CD8+ T cells, and NK cells was observed significantly in nonsurviving patients and those who were admitted to the intensive care unit in COVID-19 cancer and noncancer patients. The increased expression of PD-1 and CD95 could be possible prognostic factors for COVID-19 severity and adverse outcomes in COVID-19 cancer and noncancer patients.

Detection of abnormal lymphocytes in the peripheral blood of COVID-19 cancer patients: diagnostic and prognostic possibility.

BACKGROUND: Peripheral morphological abnormalities play important roles in the early diagnosis and prognosis of the COVID-19 infection. The aim of the present study was to assess the morphological alterations in the peripheral blood (PB) cells in patients with COVID-19 infection, with special attention to a different group of atypical lymphocytes that had been observed in the PB of COVID-19 cancer and non-cancer patients. METHODS: The PB cells were examined in 84 COVID-19 positive cancer patients, and 20 COVID-19 positive non-cancer patients, compared to 30 healthy normal controls. The data were correlated to the disease severity, patients' clinicopathological features, and outcomes. RESULTS: There was an increased incidence of giant platelets, neutrophils shifting left, and abnormal monocytes in the COVID-19 positive cancer and non-cancer patients compared to the control group (P < .001, P < .001 and P = .014; respectively). Neutrophils with abnormal toxic granulations, Pseudo Pelger-Heut abnormality, and reactive lymphocytes were significantly increased in COVID-19 cancer patients compared to COVID-19 non-cancer patients and the control group (P = .001, P < .001, and P < .001; respectively). An abnormal form of lymphocytes' morphological changes (Covicytes) was significantly detected in COVID-19 cancer patients [60.7% (51/84)], and in COVID-19 non-cancer patients [55% (11/20)], while it was absent in the normal controls [0.0% (0/30), P < 0.001]. The presence of the Covicytes is associated significantly with a better prognosis in cancer and non-cancer COVID-19 patients. CONCLUSION: Covicytes could be a useful marker supporting the diagnosis of SARS-COV-2 infection, and it is associated with a favorable prognosis.

Clinical Significance of MAP-7 and FOXC1 in Egyptian Acute Myeloid Leukemia Patients.

PURPOSE: The present study aimed to report the clinical correlations and prognostic significance of microtubule-associated protein-1 (MAP-7) and forkhead box transcription factor-C1 (FOXC1) expression in Egyptian patients with newly diagnosed acute myeloid leukemia (AML). METHODS: The study included 80 adults with newly diagnosed AML. Laboratory investigations included complete blood count, morphological examination of bone marrow aspirate, immunophenotyping, conventional karyotyping and molecular study for fms-like tyrosine kinase 3 (FLT3), nucleophosmin-1 (NPM1) and CCAAT/enhancer binding protein α (CEBPA) mutations. MAP-7 and FOXC1 expressions in bone marrow were determined using RT-PCR. Patients were followed for a median (range) period of 6.4 (1.0-35) months. The study outcomes included treatment response, progression-free survival (PFS) and overall survival (OS). RESULTS: Patients with low FOXC1 expression had significantly lower mortality rate (60.0 % versus 84.6 %, p=0.021), significantly longer PFS duration and significantly longer OS. No significant differences were noted between MAP7 expression groups regarding treatment response, mortality rate, PFS duration and OS duration. Interestingly, a significant direct correlation was noted between FOXC1 and MAP7 expressions (r=0.25, p=0.027). CONCLUSIONS: FOXC1 and MAP7 expressions are significantly correlated. High expression of FOXC1 in Egyptian population may be related to shorter OS and PFS.

Could COVID-19 induce remission of acute leukemia?

BACKGROUND: COVID-19 viral pandemic caused many mortalities in cancer patients especially those with hematological malignancies. The immunological response to COVID-19 infection is responsible for the outcome of cases whether mild, severe or critical. CASE PRESENTATION: Two cases presented with moderate COVID-19 viral infection, concomitant with acute myeloid leukemia and T acute lymphoblastic leukemia, respectively. Surprisingly, after the administration of COVID-19 supportive therapy, the cases showed disease remission after a follow-up period of 12 and 5 months, respectively. Additionally, the blast cells dropped to only 3% and 0% in the bone marrow aspirates of those two cases, respectively, after it was 30% in both cases at diagnosis. CONCLUSION: The immune response that emerged against COVID-19 infection could potentially produce anti-tumor immunity in some patients, or the virus may act as an oncolytic virus. However, further investigations are required to explain this phenomenon, which may help in finding a possible new targeted therapy for these cases.

The role of inflammatory indices in the outcome of COVID-19 cancer patients.

To assess the prognostic role of different inflammatory indices on the outcome of cancer patients with COVID-19. Sixty-two adults and 22 pediatric cancer patients with COVID-19 infection were assessed for the prognostic value of certain inflammatory indices including the neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), platelet to lymphocyte ratio (PLR), derived NLR (dNLR), systemic inflammation index (SII), mean platelet volume to platelet ratio (MPR), C-reactive protein to lymphocyte ratio (CRP/L), aggregate index of systemic inflammation (AISI), systemic inflammation response index (SIRI), and neutrophil to lymphocyte, platelet ratio (NLPR). Data were correlated to patients' outcome regarding ICU admission, and incidence of mortality. Increased CRP/L ratio in adult COVID-19 cancer patients was significantly associated with inferior survival [152 (19-2253) in non-survivors, compared to 27.4 (0.8-681) in survivors (P = 0.033)]. It achieved a sensitivity (60%) and a specificity (90.2%) at a cut-off 152, while it achieved a sensitivity of 60% and specificity 95.1% at a cut-off 252 (AUC 0.795, P = 0.033). When combining both CRP/L and NLPR for the prediction of poor outcome in adult cancer patients with COVID19, the sensitivity increased to 80% and the specificity was 70.7% (AUC 0.805, P = 0.027). Increased incidence of ICU admission in pediatric cancer patients associated significantly with the severity of covid19 infection, decreased mean corpuscular hemoglobin (MCH) < 28.3, increased red cell distribution width (RDW) > 16, lymphopenia < 1.04, pseudo Pelger-Huet appearance, and PLR < 196.4 (P = 0.004, P = 0.040, P = 0.029, P = 0. 0.039, P = 0.050, and P = 0.040; respectively). The mean corpuscular volume (MCV), MCH, and RDW could be useful prognostic markers for poor outcome in COVID-19 pediatric cancer patients (P < 0.05 for all). Increased both CRP/L and NLPR associated significantly with poor survival in adult COVID-19 cancer patients, while PLR associated significantly with ICU admission in pediatric COVID-19 cancer patients.

Prognostic Values of MicroRNA-21 and Ki-67 in Diffuse Large B-Cell Lymphoma Patients: Egyptian Experience.

BACKGROUND: MicroRNA-21 (miR-21) is a small non-coding RNA which influences tumorigenesis by inhibiting the expression of target genes. Ki-67 is a nucleolar antigen highly correlated with the rate of proliferating cells. In this study, we aimed to evaluate the prognostic impact of miR-21 and Ki-67 in DLBCL disease in a cohort of Egyptian patients. METHODS: We prospectively enrolled 53 newly diagnosed DLBCL patients. RT-PCR was used to evaluate the plasma expression levels of miR-21. Tissue Ki-67 was assessed using immunohistochemistry (IHC) of lymph node biopsy sections. Overall survival (OS) and progression free survival (PFS) were the primary outcomes. RESULTS: miR-21 expression was significantly higher in patients with DLBCL in comparison to controls (p < 0.001). The median Ki-67 expression was 70% and positivity ranged from 25% to 100%. Response to treatment was achieved in 23 patients (43.4%). Higher miR-21 was associated with poor response to treatment (p = 0.03). Although patients' age was a significant predictor of OS in univariate analysis, none of the studied factors could predict OS in multivariate analysis. However, we found that Ki-67 expression was a significant predictor of PFS in both univariate and multivariate analyses. CONCLUSIONS: The study suggested that plasma miR-21 might be a valuable non-invasive prognostic marker of response to treatment in DLBCL patients. Moreover, Ki-67 is a potential significant predictor of both OS and PFS in those patients.

Diagnostic, prognostic and predictive values of miR-100 and miR-210 in pediatric acute lymphoblastic Leukemia.

BACKGROUND: : microRNAs are playing important roles in the diagnosis and prognosis of pediatric acute lymphoblastic leukemia (ALL). METHODS: Expression levels of miR-100 and miR-210 were assessed in bone marrow aspirate of 85 pediatric ALL patients compared to 12 healthy control using quantitative real-time polymerase chain reaction. Data were correlated with relevant clinico-pathological features of the patients, response to treatment, disease-free survival (DFS), and overall survival (OS). RESULTS: miR-100 was significantly downregulated in ALL patients [median: 1.21, range: 0-434.3] compared to the control group [median: 8.41, range; 0-840.3, P = 0.035]. miR-210 was significantly upregulated in ALL patients [median: 6.34, range: 1.16-1088.7] compared to the control group [median: 2.57, range: 0.11-709.2, P = 0.025]. The sensitivity, specificity, and area under curve of miR-100 were (64.7%, 62.5%, and 0.642; respectively, P = 0.035) at a cut-off 2.6 and that of miR-210 were (60%, 58.3% and 0.650; respectively, P = 0.025) at a cut-off 3.5. miR-100 overexpression associated with shorter DFS and OS (P = 0.033 and 0.046; respectively). Patients with miR-100 lowexpression showed a significant incidence of late death ( P = 0.024). There was no significant association between miR-210 expression and DFS, OS, incidence of early or late death. CONCLUSION: : miR-100 and miR-210 could be used as potential diagnostic markers for pediatric ALL. miR-100 is a useful prognostic and predictive biomarker for childhood ALL.

Role of cyclins A and E in endometrial carcinogenesis in breast cancer patients under tamoxifen treatment.

PURPOSE: The objective of our study was to determine the relevance of cyclins A and E overexpression in endometrial carcinogenesis in hormone receptor-positive breast cancer patients under tamoxifen therapy. EXPERIMENTAL DESIGN: We assessed expression of cyclins A and E in Endometrial cytology samples collected from 36 ER and PR positive breast cancer patients; under tamoxifen treatment by using the Tao-brush non-invasive brushing cytology technique. Cyclins were detected in the collected samples by means of immuno-cytochemistry. The patients included in this study are a cohort of 36 breast cancer patients who were operated upon at the National Cancer Institute - Cairo University in the period from February 2006 to May 2008 and received tamoxifen (TAM) as part of their adjuvant treatment. RESULTS: Cyclins A and E were expressed in 17 and 15 of the 36 collected endometrial cytology samples (47.2% and 41.6% respectively). Expression of cyclins A and E was highly correlated to Tamoxifen exposure duration (32 and 43 months respectively) p < 0.001. Tamoxifen median exposure duration was shortened to 21 months in cases showing positivity for either markers, while in cases showing positivity for both cyclins, the median exposure duration was longer (44.5 months) (p < 0.001). Neither cyclin A nor E was detected before median tamoxifen exposure duration of 11 months. Endometrial carcinoma cases had the longest Tamoxifen exposure duration (60 months). CONCLUSION: Cyclins A and E expression is involved in the carcinogenesis of endometrium in women with breast cancer and under tamoxifen-treatment. Follow up of the patients using these 2 markers is highly recommended starting from the 12th month.