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Omaima I Abdel Hamid,1 Mohamed E Attia,2 Jon M Hirshon,3,4 Mohamed El-Shinawi,5,6 Moustafa El-Hussaini,7 Maged El-Setouhy7,8 1Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt; 2Orthopedics Departments, Faculty of Medicine, Zagazig University, Zagazig, Egypt; 3Department of Emergency Medicine, University of Maryland, School of Medicine, Baltimore, MD, USA; 4Department of Epidemiology and Public Health, University of Maryland, School of Medicine, Baltimore, MD, USA; 5Department of General Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 6Galala University, Galala City, Suez, Egypt; 7Department of Community, Environmental and Occupational Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 8Department of Family and Community Medicine, Faculty of Medince, Jazan University, Jazan, Kingdom of Saudi ArabiaCorrespondence: Omaima I Abdel Hamid, Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt, Tel +201001664310, Email dr_omaima2006@yahoo.comIntroduction: Hip arthroplasty (HA) using implantable metal components is among the commonest orthopedic interventions. However, it can be followed by several complications following corrosion and the release of metal ions. Several studies proved that damaged genomic DNA may contribute to the pathophysiology of mental disorders.Aim: The current work aims to evaluate the psychiatric disorders in metal on polyethylene hip arthroplasty (MOP-HA) patients and its correlation to cobalt/chromium (Co/Cr) levels and genotoxicity.Methods: The work was a longitudinal follow-up study including 34 adults with unilateral primary MOP-HA meeting the inclusion and exclusion criteria. Preoperatively, 6, 12-months-postoperatively, patients were examined for cognitive impairment using mini-mental-state-examination (MMSE), depression using major-depressive-inventory (MDI), and blood samples were collected for estimation of Co/Cr, detection of genotoxicity by single-cell-gel-electrophoresis (comet assay) and serum 8-hydroxy-2’–deoxyguanosine (8-OHdG).Results: Cognitive impairment was reported in 18.5% and 14.8% at 6-months, and 12-months postoperative, respectively. Depressive disorder was recorded in 22.2% at 6-months and 14.8% at 12-months postoperative. The marginal homogeneity tests proved a non-significant difference. There was a non-significant difference in preoperative, 6-months, 12-months postoperative MMSE, and MDI scores. There were significantly increased Co/Cr levels at 6-months postoperative. The levels decreased at 12-months postoperative, however, still significantly higher than preoperative values. There was a significant increase in serum 8-OHdG and the levels were positively correlated to cobalt levels at both 6 and 12-months-postoperative. There was a non-significant difference among preoperative, 6-months, and 12-months postoperative comet assay measurements.Conclusion: From previous findings, we can conclude that will-functioning MOP hip arthroplasty can induce increased ion levels and positively correlated increase in biochemical markers of genotoxicity (8-OHdG).Keywords: metal on polyethylene hip arthroplasty, cobalt, chromium, major depressive inventory, mini-mental state examination, genotoxicity

Manar M Ellaban,1 Eman Afifi,2 Moustafa El Houssinie,1 Jon Mark Hirshon,3,4 Mohamed El-Shinawi,3,5,6 Maged El-Setouhy1,3,7 1Department of Community, Environmental and Occupational Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 2Department of Geriatrics and Gerontology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 3Department of Emergency Medicine, University of Maryland School of Medicine, Baltimore, MD, USA; 4Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA; 5General Surgery Department, Ain Shams University, Cairo, Egypt; 6Galala University, Cairo, Egypt; 7Department of Family and Community Medicine, Faculty of Medicine, Jazan University, Jazan, Saudi ArabiaCorrespondence: Manar M EllabanCommunity, Environmental and Occupational Medicine, Faculty of Medicine, Ain Shams University, Abbasia, Cairo, EgyptTel +201550690740Fax +2024346041Email manarellaban@med.asu.edu.egPurpose: For knife-related injuries (KRI), a comprehensive understanding of the incidence, mechanism, and pattern of injury is required for the development of prevention strategies. Unfortunately, reliable data on knife-related injuries are difficult to obtain. In Egypt, there is no national routine surveillance system for all knife injuries. The aim was to examine the epidemiologic characteristics of knife-related injuries at the Ain Shams University Hospital (ASUH) emergency department (ED).Patients and Methods: A cross-sectional study was conducted on 140 patients who presented with knife injuries at the ASUH ED. Data collection was done during a randomly selected period of seven days each month from October 2018 to September 2019. The sociodemographic characteristics, injury-related variables, and outcomes of the injury were recorded on a structured worksheet.Results: Knife-related injuries represented 22.9% of all injury cases that presented to the ED. Majority of the knife-related injuries (87.86%) were accidental, 7.9% were assault, and 4.3% were self-inflicted. Home was the most reported place of injury. Most of the victims were discharged from the ED (87.1%), and 84.3% recovered completely. The mean hospital stay was 3.6 ± 1.3 days.Conclusion: Majority of the knife-related injuries were accidental, and the most common pattern was isolated chest injury with contusions. Cases that were not severe and had favorable prognosis (ie, complete recovery) comprised the largest proportion. Recommendations include development of a surveillance system may result in the effective control and prevention of this growing problem of knife-related injuries.Keywords: epidemiology, knife injuries, accidental, emergency department, ASUH

Mahmoud Farghaly,1 Abdallah Kamal,1,2 Maged El-Setouhy,3,4 Jon Mark Hirshon,5,6 Mohamed El-Shinawi1,7 1Department of General Surgery, Ain Shams University, Cairo, Egypt; 2Department of Radiology, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA; 3Department of Community, Environmental and Occupational Medicine, Ain Shams University, Cairo, Egypt; 4Department of Family and Community Medicine, Jazan University, Jazan, Saudi Arabia; 5Department of Emergency Medicine, University of Maryland School of Medicine, Baltimore, MD, USA; 6Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA; 7Department of Medical Education, Galala University, Cairo, EgyptCorrespondence: Mahmoud FarghalyDepartment of General Surgery, Ain Shams University, Cairo, EgyptTel +20 1001775378Email Mahmoudfarghali@med.asu.edu.egStudy Design: Retrograde cross-sectional study.Objective: To assess patient satisfaction and outcomes in polytraumatized patients in EL-Demerdash hospital.Background: This is the first study that assessed patient satisfaction with a tertiary hospital in Egypt. Ain Shams University Surgery Hospital, which is one of the largest hospitals in Egypt and serves millions of patients each year, was the site of the study.Methods: A version of the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey was used to query 361 patients from November 2015 until July 2018 Survey questions were divided into the following categories: communication with doctors, responsiveness of hospital staff, cleanliness of the hospital environment, quietness of the hospital environment, pain management, communication about medicines, discharge information, overall rating of the hospital, and willingness to recommend the hospital.Results: A total of 361 patients were interviewed. The results showed both positive and negative levels of satisfaction. The positive results included no delay in admission, friendly staff including nurses and doctors, better patient outcomes regarding pain management and adverse side effects, and the overall rating of the hospital was good, which reflected patient satisfaction. The negative findings were lack of proper communication between the medical staff and patients. Patients indicated they did not get a satisfactory explanation of their prescribed drug doses and drug adverse effects. In addition, they did not get enough instruction on what to do after being released from the hospital.Conclusion: The medical staff at Ain Shams University Surgery Hospital should focus more on the patient’s own preferences and communicate better with patients. We recommended that the hospital organize regular communication skills courses for medical students, physicians, and nurses. Patients should understand the discharge report and indications and side effects of the medications before leaving the hospital.Keywords: HCAHPS, quality, patients’ satisfaction, community

Background: Leukocytes plays crucial role in breast cancer progression and lymph node metastasis. Veins draining the breast through the axillary tributaries contain tumor-associated leukocytes migrating away from tumor microenvironment. Collecting tumor-associated leukocytes and characterizing their immunophenotype and biological properties in positive and negative lymph node patients may elucidate their role in lymph node metastasis. Aims: Using an innovative surgical approach previously described, we collected tumor-associated leukocytes from venous drainage of the breast during breast cancer surgery of positive and negative lymph node (LN)metastasis patients. Isolated leukocytes were subjected to: 1) immunophenotyping; 2) cytokine profiling; and 3) assessment of the expression level of total and phospho NF-kβ. Material and Methods: We enrolled 40 patients diagnosed with breast cancer from Ain Shams University Hospitals. Patients were sub-grouped into negative (zero) and positive (4) LN metastasis patients. All enrolled patients had not received neo-adjuvant chemotherapy. During modified radical mastectomy or conservative breast surgery, 15--20 ml of blood were collected from axillary vein tributaries for the isolation of tumor-associated leukocytes by Ficoll- Hypaque density gradient centrifugation. The immunophenotype of the isolated mononuclear cells was assessed using flow cytometry to identify the percentage of T lymphocytes (CD3+) and their subpopulations (CD4+ and CD8+), NK cells (CD56+) and B-lymphocytes (CD19+). Tumor-associated leukocytes isolated from positive and negative LN patients were seeded overnight in appropriate culture media at 37°C in a humidified CO2 incubator. Conditioned media containing secreted cytokines/chemokines were profiled using RayBio human cytokine antibody arrayIIIand then analyzed and quantified using ImageJ software. In addition, using immunoblotting we assessed the level of expression of total and phospho NF-kβ in leukocyte lysates from positive and negative LN patients. Result: Flow cytometric analysis revealed a significant increase in the percentage of T lymphocytes and T helper(CD3+/CD4+) cells collected from axillary tributaries of positive LN patients as compared to negative LN patients. Leukocytesisolated from positive LN patients were characterized by more than five-foldincreases in IL-12, Thrombopoietin, IL-13, INF-γ , TARC, IGF-1, IL-3, TNF-α, IL-4, GCSF, IL-5 and IL-1α. Moreover, we detected an increase in cellular expression of total and phospho NF-kβ in leukocytes isolated from positive LN as compared to negative LN breast cancer patients. Conclusion: Our results demonstrate for the first time that tumor-associated leukocytes of positive LN patients possess different cytokine patterns than those of negative LN patients. Moreover, we identified major cytokines that may contribute to LN metastasis and could be therapeutically targeted. [ABSTRACT FROM AUTHOR]

Abstract Background Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. In non-IBC, the cysteine protease cathepsin B (CTSB) is known to be involved in cancer progression and invasion; however, very little is known about its role in IBC. Methods In this study, we enrolled 23 IBC and 27 non-IBC patients. All patient tissues used for analysis were from untreated patients. Using immunohistochemistry and immunoblotting, we assessed the levels of expression of CTSB in IBC versus non-IBC patient tissues. Previously, we found that CTSB is localized to caveolar membrane microdomains in cancer cell lines including IBC, and therefore, we also examined the expression of caveolin-1 (cav-1), a structural protein of caveolae in IBC versus non-IBC tissues. In addition, we tested the correlation between the expression of CTSB and cav-1 and the number of positive metastatic lymph nodes in both patient groups. Results Our results revealed that CTSB and cav-1 were overexpressed in IBC as compared to non-IBC tissues. Moreover, there was a significant positive correlation between the expression of CTSB and the number of positive metastatic lymph nodes in IBC. Conclusions CTSB may initiate proteolytic pathways crucial for IBC invasion. Thus, our data demonstrate that CTSB may be a potential prognostic marker for lymph node metastasis in IBC.

Background: Trauma is a significant cause of mortality, especially among individuals aged between 15 and 44 years, with a substantial burden falling on economically active populations. Low- and middle-income countries (LMICs) bear the burden of trauma-related deaths, accounting for over 90 % globally. In Egypt, trauma rates are increasing, primarily due to road traffic crashes (RTC), affecting males disproportionately. Blunt abdominal trauma, often caused by RTC, can lead to missed intra-abdominal injuries (IAIs) due to atypical symptoms. Computed Tomography (CT) offers high sensitivity and specificity in detecting IAIs, but concerns about cost and radiation exposure exist., Methodology: This study investigates the roles of Focused Assessment with Sonography for Trauma (FAST) and CT in managing blunt abdominal trauma. A retrospective cohort study was conducted on hemodynamically stable patients. Data included patient demographics, trauma details, healthcare decisions, costs, and outcomes., Results: Computed tomography significantly reduced unnecessary laparotomies (12.3% vs. 24.8 %, p = 0.001), shortened hospital stays (4.83±0.71 days vs. 6.15±1.28 days, p = 0.005), and reduced ICU admissions (8 vs. 32, p = 0.023) compared to FAST alone. Overall costs were lower in the CT & FAST Group ($2055.95 vs. $3488.7, p = 0.0001), with no significant difference in missed IAIs., Conclusion: This study highlights the limitations of relying solely on FAST for IAIs and underscores the value of CT in guiding healthcare decisions. Incorporating CT led to reduced negative laparotomies, shorter hospital stays, and fewer ICU admissions. While CT incurs initial costs, its long-term benefits outweigh expenditures, particularly in LMICs. This study provides insights into optimizing diagnostic approaches for blunt abdominal trauma in low-resource settings., Competing Interests: This research was funded throughout all its steps by the Fogarty Institute, USA. The authors declared no other conflicts of interest., (© 2023 The Authors. Published by Elsevier B.V. on behalf of African Federation for Emergency Medicine.)

Introduction: Chest imaging plays a prominent role in the assessment of patients with blunt trauma. Selection of the right approach at the right time is fundamental in the management of patients with blunt chest trauma . [1] A reliable, economic, bedside, and rapidly accomplished screening test can be pivotal. [2]., Objective: The aim of this study was to compare the accuracy of extended- focused assessment with sonography for trauma (E-FAST) to that of the National Emergency X-Radiography Utilisation Study (NEXUS) chest algorithm in detecting blunt chest injuries., Methods: This descriptive cross-sectional study included 50 polytrauma patients with blunt chest trauma from the emergency centre of Suez Canal University Hospital. E-FAST and computed tomography (CT) were conducted, followed by reporting of NEXUS criteria for all patients. Blinding of the E-FAST performer and CT reporter were confirmed. The results of both the NEXUS algorithm and E-FAST were compared with CT chest results., Results: The NEXUS algorithm had 100% sensitivity and 15.3% specificity, and E-FAST had 70% sensitivity and 96.7% specificity, in the detection of pneumothorax.In the detection of hemothorax, the sensitivity and specificity of the NEXUS algorithm were 90% and 7.5%, respectively, whereas E-FAST had a lower sensitivity of 80% and a higher specificity of 97.5%., Conclusion: E-FAST is highly specific for the detection of hemothorax, pneumothorax, and chest injuries compared with the NEXUS chest algorithm, which demonstrated the lowest specificity. However, the NEXUS chest algorithm showed a higher sensitivity than E-FAST and hence can be used effectively to rule out thoracic injury., Competing Interests: This work was funded by the National Institutes of Health, Fogarty International Center, Bethesda, MD (grant number, 2D43TW007296). The authors declare that they have no other competing interests., (© 2023 The Authors. Published by Elsevier B.V. on behalf of African Federation for Emergency Medicine.)

Background: Matricellular proteins comprising matrisome and adhesome are responsible for structure integrity and interactions between cells in the tumour microenvironment of breast cancer. Changes in the gene expression of matrisome and adhesome augment metastasis. Since inflammatory breast cancer (IBC) is characterized by high metastatic behaviour. Herein, we compared the gene expression profile of matrisome and adhesome in non-IBC and IBC in fresh tissue and ex vivo patient-derived explants (PDEs) and we also compared the secretory inflammatory mediators of PDEs in non-IBC and IBC to identify secretory cytokines participate in cross-talk between cells via interactions with matrisome and adhisome., Methods: Fifty patients (31 non-IBC and 19 IBC) were enrolled in the present study. To test their validation in clinical studies, PDEs were cultured as an ex vivo model. Gene expression and cytokine array were used to identify candidate genes and cytokines contributing to metastasis in the examined fresh tissues and PDEs. Bioinformatics analysis was applied on identified differentially expressed genes using GeneMANIA and Metascape gene annotation and analysis resource to identify pathways involved in IBC metastasis., Results: Normal and cancer fresh tissues and PDEs of IBC were characterized by overexpression of CDH1 and MMP14 and downregulation of CTNNA1 and TIMP1 compared with non-IBC. The secretome of IBC cancer PDEs is characterized by significantly high expression of interleukin 6 and monocyte chemoattractant protein-1 (CCL2) compared with non-IBC., Conclusion: Genes expressed by adhisome and matrisome play a significant role in IBC metastasis and should be considered novel target therapy., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Emergency medicine (EM) was formally recognized as a specialty in Egypt in 2002. Many institutions of higher education do not yet have an operational academic department of emergency medicine. This study attempts to quantify the awareness and attitude of Ain Shams University medical students towards emergency medicine as both a specialty and a career., Methods: A paper-based survey was delivered to undergraduate medical students at the Faculty of Medicine, Ain Shams University in Cairo, Egypt between December 2021 and April 2022. The survey was designed to assess awareness towards the scope of practice of emergency physicians as well as general attitude toward emergency medicine as a specialty and career choice., Results: A total of 391 students and interns/house officers participated in this study. 53.2% of participants were females and the mean age was 21.65 ± 2.25 years. Only 30 participants (7.7%) were classified as having "Excellent knowledge" of emergency medicine, 92 (23.5%) as "Good knowledge", 158 "40.4%" as "Fair knowledge" and 111 (28.4%) as "Poor knowledge". The difference in scores between academic years was not statistically significant (p = 0.239). 91.8% of respondents favored the creation of student interest groups in EM and 40% of respondents found it difficult to reach information regarding EM., Conclusion: Our study demonstrates a lack of awareness and knowledge towards emergency medicine as a specialty across all academic years at our institution. Formal recognition of EM as a specialty doesn't guarantee widespread knowledge among medical students, particularly at institutions without academic EM departments., Competing Interests: The authors declared no conflicts of interest., (© 2022 The Authors. Published by Elsevier B.V. on behalf of African Federation for Emergency Medicine.)

Background Blunt abdominal trauma (BAT) is the most common pattern of abdominal traumas. It may be associated with intra-abdominal injuries (IAIs). Exploratory laparotomies are only needed in a minority of patients after BAT. Methodology All BAT patients who presented to the El Demerdash Hospital of Ain Shams University, Cairo, Egypt during the study period were traced. Parameters including demographic data, focused assessment with sonography for trauma (FAST) scan, CT scan results, and hematuria were collected. The cohort was divided according to the CT scan results into two groups: patients with IAIs and patients without IAIs. Results Males represented 78.2% of the patients, and the mean age of the recruited patients was 32.1 ± 18 years. Road traffic accidents represented the main cause of trauma (58%) . Patients with IAIs detected by CT scan represented 1.62%, and hematuria was detected in 88.9% of them. The specificity of FAST was 97.1%, and that of hematuria was 84.1%, and for the combination of both tests, the specificity was 99.3%. Conclusion IAIs after BAT can usually be excluded if both FAST and hematuria are negative, provided that the patient is stable., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Abd-erRazik et al.)

Studies suggested that the pathogenesis of inflammatory breast cancer (IBC) is related to inflammatory manifestations accompanied by specific cellular and molecular mechanisms in the IBC tumor microenvironment (TME). IBC is characterized by significantly higher infiltration of tumor-associated macrophages (TAMs) that contribute to its metastatic process via secreting many cytokines such as TNF, IL-6, IL-8, and IL-10 that enhance invasion and angiogenesis. Thus, there is a need to first understand how IBC-TME modulates the polarization of TAMs to better understand the role of TAMs in IBC. Herein, we used gene expression signature and Synchrotron Fourier-Transform Infrared Microspectroscopy (SR-μFTIR) to study the molecular and biochemical changes, respectively of in vitro polarized TAMs stimulated by the secretome of IBC and non-IBC cells. The gene expression signature showed significant differences in the macrophage's polarization-related genes between stimulated TAMs. FTIR spectra showed absorption bands in the region of 1700-1500 cm -1 attributed to the amide I ν(C=O), & ν AS (CN), δ (NH), and amide II ν(CN), δ (NH) proteins bands. Moreover, three peaks of different intensities and areas were detected in the lipid region of the νCH 2 and νCH 3 stretching modes positioned within the 3000-2800 cm -1 range. The PCA analysis for the second derivative spectra of the amide regions discriminates between stimulated IBC and non-IBC TAMs. This study showed that IBC and non-IBC TMEs differentially modulate the polarization of TAMs and SR-μFTIR can determine these biochemical changes which will help to better understand the potential role of TAMs in IBC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Inflammatory breast cancer (IBC) represents a deadly aggressive phenotype of breast cancer (BC) with a unique clinicopathological presentation and low survival rate. In fact, obesity represents an important risk factor for BC. Although several studies have identified different cellular-derived and molecular factors involved in IBC progression, the role of adipocytes remains unclear. Cancer-associated adipose tissue (CAAT) expresses a variety of adipokines, which contribute to tumorigenesis and the regulation of cancer stem cell (CSC). This research investigated the potential effect of the secretome of CAAT explants from patients with BC on the progression and metastasis of the disease., Methods: This study established an ex-vivo culture of CAAT excised from IBC (n = 13) vs. non-IBC (n = 31) patients with obesity and profiled their secretome using a cytokine antibody array. Furthermore, the quantitative PCR (qPCR) methodology was used to validate the levels of predominant cytokines at the transcript level after culture in a medium conditioned by CAAT. Moreover, the impact of the CAAT secretome on the expression of epithelial-mesenchymal transition (EMT) and cells with stem cell (CSC) markers was studied in the non-IBC MDA-MB-231 and the IBC SUM-149 cell lines. The statistical differences between variables were evaluated using the chi-squared test and unpaired a Student's t-test., Results: The results of cytokine array profiling revealed an overall significantly higher level of a panel of 28 cytokines secreted by the CAAT ex-vivo culture from IBC patients with obesity compared to those with non-IBC. Of note, interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemo-attractant protein 1 (MCP-1) were the major adipokines secreted by the CAAT IBC patients with obesity. Moreover, the qPCR results indicated a significant upregulation of the IL-6, IL-8, and MCP-1 mRNAs in CAAT ex-vivo culture of patients with IBC vs. those with non-IBC. Intriguingly, a qPCR data analysis showed that the CAAT secretome secretions from patients with non-IBC downregulated the mRNA levels of the CD24 CSC marker and of the epithelial marker E-cadherin in the non-IBC cell line. By contrast, E-cadherin was upregulated in the SUM-149 cell., Conclusions: This study identified the overexpression of IL-6, IL-8, and MCP-1 as prognostic markers of CAAT from patients with IBC but not from those with non-IBC ; moreover, their upregulation might be associated with IBC aggressiveness via the regulation of CSC and EMT markers. This study proposed that targeting IL-6, IL-8, and MCP-1 may represent a therapeutic option that should be considered in the treatment of patients with IBC., (© 2022. The Author(s).)

Inflammatory breast cancer (IBC) is a highly aggressive phenotype of breast cancer that is characterized by a high incidence early metastasis. We previously reported a significant association of human cytomegalovirus (HCMV) DNA in the carcinoma tissues of IBC patients but not in the adjacent normal tissues. HCMV-infected macrophages serve as "mobile vectors" for spreading and disseminating virus to different organs, and IBC cancer tissues are highly infiltrated by tumor-associated macrophages (TAMs) that enhance IBC progression and promote breast cancer stem cell (BCSC)-like properties. Therefore, there is a need to understand the role of HCMV-infected TAMs in IBC progression. The present study aimed to test the effect of the secretome (cytokines and secreted factors) of TAMs derived from HCMV + monocytes isolated from IBC specimens on the proliferation, invasion, and BCSC abundance when tested on the IBC cell line SUM149. HCMV + monocytes were isolated from IBC patients during modified radical mastectomy surgery and tested in vitro for polarization into TAMs using the secretome of SUM149 cells. MTT, clonogenic, invasion, real-time PCR arrays, PathScan Intracellular Signaling array, and cytokine arrays were used to characterize the secretome of HCMV + TAMs for their effect on the progression of SUM149 cells. The results showed that the secretome of HCMV + TAMs expressed high levels of IL-6, IL-8, and MCP-1 cytokines compared to HCMV - TAMs. In addition, the secretome of HCMV + TAMs induced the proliferation, invasion, colony formation, and expression of BCSC-related genes in SUM149 cells compared to mock untreated cells. In addition, the secretome of HCMV + TAMs activated the phosphorylation of intracellular signaling molecules p-STAT3, p-AMPKα, p-PRAS40, and p-SAPK/JNK in SUM149 cells. In conclusion, this study shows that the secretome of HCMV + TAMs enhances the proliferation, invasion, colony formation, and BCSC properties by activating the phosphorylation of p-STAT3, p-AMPKα, p-PRAS40, and p-SAPK/JNK intracellular signaling molecules in IBC cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mohamed, El-Sharkawy, El-Shinawi, Schneider and Mohamed.)

Inflammatory breast cancer (IBC) is an aggressive phenotype with a high recurrence and low survival rate. Approximately 90% of local breast cancer recurrences occur adjacent to the same quadrant as the initial cancer, implying that tumor recurrence may be caused by residual cancer cells and/or quiescent cancer stem cells (CSCs) in the tumor. We hypothesized that wound fluid (WF) collected after modified radical mastectomy (MRM) may activate cancer cells and CSCs, promoting epithelial mesenchymal transition (EMT) and invasion. Therefore, we characterized the cytokinome of WF drained from post-MRM cavities of non-IBC and IBC patients. The WF of IBC patients showed a significantly higher expression of various cytokines than in non-IBC patients. In vitro cell culture models of non-IBC and IBC cell lines were grown in media conditioned with and/without WF for 48 h. Afterwards, we assessed cell viability, the expression of CSCs and EMT-specific genes, and tumor invasion. Genes associated with CSCs properties and EMT markers were regulated in cells seeded in media conditioned by WF. IBC-WF exhibited a greater potential for inducing IBC cell invasion than non-IBC cells. The present study demonstrates the role of the post-surgical tumor cavity in IBC recurrence and metastasis.

Introduction: Trauma deaths account for 8% of all deaths in Egypt. Patients with multiple injuries are at high risk but may be saved with a good triage system and a well-trained trauma team in dedicated institutions. The incidence of missed injuries in the Emergency Centre (EC) of Suez Canal University Hospital (SCUH) was found to be 9.0% after applying Advanced Trauma Life Support (ATLS) guidelines. However, this rate is still high compared with many trauma centers., Aim: Improve the quality of management of polytrauma patients by decreasing the incidence of missed injuries by implementing the Sequential Trauma Education Programs (STEPs) course in the EC at SCUH., Methods: This interventional training study was conducted in the SCUH EC that adheres to CONSORT guidelines. The study was conducted during the one month precourse and for 6 months after the implementation of the STEPs course for EC physicians. Overall, 458 polytrauma patients were randomly selected, of which 45 were found to have missed injuries after applying the inclusion and exclusion criteria. We assessed the clinical relevance of these cases for missed injuries before and after the STEPs course., Results: Overall, 45 patients were found to have missed injuries, of which 15 (12%) were pre-STEPs and 30 (9%) were post-STEPs course. The STEPs course significantly increased adherence to vital data recording, but the reduction of missed injuries (3.0%) was not statistically significant in relation to demographic and trauma findings. However, the decrease in missed injuries in the post-STEPs course group was an essential clinically significant finding., Conclusion: STEPs course implementation decreased the incidence of missed injuries in polytrauma patients. Thus, the STEPs course can be considered at the same level of other advanced trauma courses as a training skills program or possibly better in dealing with trauma patients. Repetition of this course by physicians should be mandatory to prevent more missed injuries. Therefore, the validation of STEPs course certification should be completed at least every two years to help decrease the number of missed injuries, especially in low-income countries and low-resource settings., (© 2022 The Authors. Published by Elsevier B.V. on behalf of African Federation for Emergency Medicine.)

Background: Workplace violence (WPV) has been recognized as a major occupational hazard worldwide. Healthcare professions are particularly at a higher risk of WPV. Patients and their relatives are commonly the most common perpetrators for WPV against physicians. Trainings on the universal precautions of violence, how to effectively anticipate, recognize and manage potentially violent situation is recommended by OSHA as a part of a written, effective, comprehensive, and interactive WPV prevention program., Objective: To implement and evaluate the effectiveness of a training session delivered to nurses. The training session aimed to increase nurses' ability to identify potentially violent situations and to effectively manage these situations in a teaching hospital in Egypt., Methodology: A total of 99 nurses attended the training sessions. Confidence in coping with aggressive patient scale, along with nurses' attitudes toward WPV, were used to assess the effectiveness of the training sessions., Results: Nurses' perceived confidence to deal with aggression increased after attending the training sessions. Nurses' attitudes toward WPV positively changed after attending the training session., Conclusion and Recommendations: Increasing awareness of the problem among healthcare professions as well as the public is warranted. Violence prevention program with a zero-tolerance policy is warranted., (© 2022. The Author(s).)

Background: 'Voodoo' is a new substance of abuse that recently spread among youth in Egypt. It has numerous potentially dangerous effects on humans. However, to date the composition of the main constituents of this compound is unknown., Purpose: We sought to identify the active components of this unknown substance"voodoo"., Methods: Three samples were collected and analysed by high-performance liquid chromatography with photodiode array detector (HPLC-PAD), gas chromatography/mass spectrometry (GC/MS), and ultra-performance liquid chromatography/mass spectrometry (UPLC-MS/MS) using targeted multiple reaction monitoring (MRM)., Results: HPLC-PAD analysis showed that samples 1 and 2 had some common major peaks, the same retention time, and similar spectra, whereas sample 3 showed different peaks. GC/MS analysis revealed the presence of various putatively identified bioactive compounds, including quinazolines, morphinan alkaloid, cannabinoids, penitrem A, and the well-known synthetic cannabinoid FUB-AMB (methyl(2S)-2-{[1-[(4-fluorophenyl)methyl]indazole-3-carbonyl]amino}-3 methylbutanoate). UPLC-MS/MS analysis revealed the presence of common compounds such as tetrahydrocannabinol (THC), amphetamine, 3,4-methylenedioxyamphetamine, tramadol, and oxazepam., Conclusion: We concluded that Voodoo is a mixture of substances of abuse at varying concentrations., Competing Interests: Disclosure statement No potential conflict of interest was reported by the authors.

Introduction: "Delayed discharge" is defined as patients who remain hospitalised beyond the time of being fit for discharge after a decision of discharge has been made by the managing team. There is no standardised amount of time defining delayed discharge documented in the literature, and there is a lack of evidence about this topic in Egypt. This study is a quality improvement project aiming to identify the factors associated with discharge delays at a single centre in Egypt in order to address this issue., Methods: A prospective observational study included all trauma patients admitted to a University Hospital in Egypt over two months. The time of the decision of discharge and actual discharge time were recorded by reviewing patients' medical records. The patients and their caregivers were asked to fill in a questionnaire about the reasons for delayed discharge. Potential reasons for the delayed discharge were classified into system-related, medical and family-related factors., Results: The study included 498 patients with a median age of 41 years (9-72). The median time from discharge decision until actual discharge was 3 h. System-related factors were documented in 48.8% of cases, followed by medical factors (36.3%), and family-related factors (28.1%). When controlling for age, gender and injury severity score using a logistic regression analysis, longer time to discharge (≥3 h) showed a stronger association with medical factors [adjusted OR (95% CI) = 5.44 (2.73-10.85)] and family-related factors [adjusted OR (95% CI) = 7.94 (3.40-18.54)] compared to system-related factors [adjusted OR (95% CI) = 2.20 (1.12-4.29)]., Discussion: Although system-related factors were more prevalent, medical and family-related factors appear to be associated with longer discharge delays compared to system-related factors., Competing Interests: The authors declare no conflicts of interest., (© 2018 Published by Elsevier Ltd. CC BY 4.0.)

Locally advanced breast cancer (LABC) is an aggressive disease characterized by late clinical presentation, large tumor size, treatment resistance and low survival rate. Expression of EGFR/HER2 and activation of intracellular tyrosine kinase domains in LABC are associated with poor prognosis. Thus, target therapies such as the anti-receptor tyrosine kinases lapatinib drug have been more developed in the past decade. The response to lapatinib involves the inhibition of RTKs and subsequently signaling molecules such as Src/STAT3/Erk1/2 known also to be activated by the cytokines in the tumor microenvironment (TME). The aim of the present study is to identify the major cytokine that might contribute to lapatinib resistance in EGFR+/HER2+ LABC patients. Indeed, tumor associated macrophages (TAMs) are the main source of cytokines in the TME. Herein, we isolated TAMs from LABC during modified radical mastectomy (MRM). Cytokine profile of TAMs revealed that IL-8 is the most prominent highly secreted cytokine by TAMs of LABC patients. Using in-vitro cell culture model we showed that recombinant IL-8 (50 and 100 ng/mL) at different time intervals interfere with lapatinib action via activation of Src/EGFR and signaling molecules known to be inhibited during treatment. We proposed that to improve LABC patients' response to lapatinib treatment it is preferred to use combined therapy that neutralize or block the action of IL-8., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Inflammatory breast cancer (IBC) is a rare, but aggressive entity of breast carcinoma with rapid dermal lymphatic invasion in young females. It is either poorly or misdiagnosed as mastitis because of the absence of a distinct lump. Small extracellular vesicles (sEVs) circulating in liquid biopsies are a novel class of minimally invasive diagnostic alternative to invasive tissue biopsies. They modulate cancer progression via shuttling their encapsulated cargo including microRNAs (miRNAs) into recipient cells to either trigger signaling or induce malignant transformation of targeted cells. Plasma sEVs < 200 nm were isolated using a modified cost-effective polyethylene glycol (PEG)-based precipitation method and compared to standard methods, namely ultracentrifugation and a commercial kit, where the successful isolation was verified by different approaches. We evaluated the expression levels of selected sEV-derived miR-181b-5p, miR-222-3p and let-7a-5p using quantitative real PCR (qPCR). Relative to non-IBC, our qPCR data showed that sEV-derived miR-181b-5p and miR-222-3p were significantly upregulated, whereas let-7a-5p was downregulated in IBC patients. Interestingly, receiver operating characteristic (ROC) curves analysis revealed that diagnostic accuracy of let-7a-5p alone was the highest for IBC with an area under curve (AUC) value of 0.9188, and when combined with miR-222-3p the AUC was improved to 0.973. Further, 38 hub genes were identified using bioinformatics analysis. Together, circulating sEV-derived miR-181b-5p, miR-222-3p and let-7a-5p serve as promising non-invasive diagnostic biomarkers for IBC., Competing Interests: The authors have declared that no competing interests exist.

Background: Breast cancer treatment is an established cause of financial toxicity, and associated costs may contribute to higher mortality and morbidity rates. In Egypt, breast cancer incidence and mortality rates are among the highest in the Middle East. Late-stage diagnosis is common, and disease occurs at an earlier age than in Europe and North America. Out-of-pocket payments are the primary means of financing healthcare in Egypt, and socioeconomic factors have been shown to significantly impact access to cancer screening and treatment., Methods: An observational cross-sectional study was conducted among breast cancer patients at Ain Shams University Hospitals in Cairo from 2013 to 2015., Results: One hundred women with breast cancer participated. There was a high need for financial assistance (66.0%) and patients with financial needs had great difficulty affording medications (80.0%). A number of patients had lost their jobs following diagnosis, with 32.7% employed prior to diagnosis and 15.3% afterwards. Nearly one-half of participants were classified as food insecure, and nearly one-third reported difficulty affording transportation costs., Conclusions: This is the first study to describe socioeconomic needs and financial impact among a cohort of Egyptian women undergoing breast cancer treatment. The findings highlight the financial impact of breast cancer treatment on a cohort of Egyptian breast cancer patients and the need for a multidisciplinary approach to help them access and mitigate the costs of treatment. Recommendations include implementing patient financial navigation services and producing printed materials to inform patients of resources to help mitigate the treatment's financial impact.

Introduction: Despite agreement in the literature that "stable" blunt trauma patients may be managed conservatively, in Egypt many such patients receive operative management. This paper presents the results of a pragmatic, prospective, observational study to evaluate outcomes of non-operative (NOP) versus operative (OP) management of blunt abdominal solid organ trauma in hemodynamically stable adults admitted to Tanta University Emergency Hospital (TUH) in Egypt., Methods: A prospective observational study enrolled adult blunt abdominal trauma patients with solid organ injury at TUH over a 3-year period (June 2014-June 2017). Inclusion criteria were age ≥18 yr, mean arterial pressure >65 mm Hg, heart rate <110 bpm, hematocrit ≥7 mg/dl, and abdominal organ injury diagnosed by ultrasound or computed tomography (CT). Excluded patients were those with pelvis and femur fractures; patients with penetrating abdominal trauma; predominate burn injuries, children and pregnant women. All patients were assigned to non-operative or operative management based on clinician preference. Outcomes of interest were 30-day mortality, blood transfusion volume, and length of stay. Descriptive statistics and χ 2 were used to compare outcomes., Results: During the study period, 4254 trauma patients presented to TUH. Of these, 790 had blunt abdominal trauma and 111 (14.1%) met inclusion criteria. Injury severity scores for each group were comparable (24 ± 10 - NOP vs. 28 ± 11 - OP, p  = 0.126). NOP received less transfused blood (213.41 ± 360.3 ml [NOP] vs.1155.17 ± 380.4 ml [OP] ( p  < 0.0001)) but had a longer length of stay (8.29 ± 2.8 [NOP] vs. 6.45 ± 1.97 days [OP] ( p  = 0.012)). There was no difference in mortality between groups ( p  = 0.091)., Conclusion: Our study demonstrated that non-operative management in Egypt of blunt abdominal trauma was safe and resulted in fewer procedures, fewer units of blood transfused, and no increase in mortality. Longer length of stay for non-operative patients might reflect treating physician caution in their management., (© 2020 African Federation for Emergency Medicine. Publishing services provided by Elsevier.)

Background: More than half of deaths in low- and middle-income countries (LMICs) result from conditions that could be treated with emergency care - an integral component of universal health coverage (UHC) - through timely access to lifesaving interventions., Methods: The World Health Organization (WHO) aims to extend UHC to a further 1 billion people by 2023, yet evidence supporting improved emergency care coverage is lacking. In this article, we explore four phases of a research prioritisation setting (RPS) exercise conducted by researchers and stakeholders from South Africa, Egypt, Nepal, Jamaica, Tanzania, Trinidad and Tobago, Tunisia, Colombia, Ethiopia, Iran, Jordan, Malaysia, South Korea and Phillipines, USA and UK as a key step in gathering evidence required by policy makers and practitioners for the strengthening of emergency care systems in limited-resource settings., Results: The RPS proposed seven priority research questions addressing: identification of context-relevant emergency care indicators, barriers to effective emergency care; accuracy and impact of triage tools; potential quality improvement via registries; characteristics of people seeking emergency care; best practices for staff training and retention; and cost effectiveness of critical care - all within LMICs., Conclusions: Convened by WHO and facilitated by the University of Sheffield, the Global Emergency Care Research Network project (GEM-CARN) brought together a coalition of 16 countries to identify research priorities for strengthening emergency care in LMICs. Our article further assesses the quality of the RPS exercise and reviews the current evidence supporting the identified priorities.

Inflammatory breast cancer (IBC) is a highly metastatic and lethal breast cancer. As many as 25-30% of IBCs are triple negative (TN) and associated with low survival rates and poor prognosis. We found that the microenvironment of IBC is characterized by high infiltration of tumor associated macrophages (TAMs) and by over-expression of the cysteine protease cathepsin B (CTSB). TAMs in IBC secrete high levels of the cytokines interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1/CCL2) compared to non-IBC patients. Herein, we tested the roles of IL-8 and MCP-1/CCL2 in modulating proteolytic activity and invasiveness of TN-non-IBC as compared to TN-IBC and addressed the underlying molecular mechanism(s) for both cytokines. Quantitative real time PCR results showed that IL-8 and MCP-1/CCL2 were significantly overexpressed in tissues of TN-IBCs. IL-8 and MCP-1/CCL2 induced CTSB expression and activity of the p-Src and p-Erk1/2 signaling pathways relevant for invasion and metastasis in TN-non-IBC, HCC70 cells and TN-IBC, SUM149 cells. Dasatinib, an inhibitor of p-Src, and U0126, an inhibitor of p-Erk1/2, down-regulated invasion and expression of CTSB by HCC70 and SUM149 cells, a mechanism that is reversed by IL-8 and MCP-1/CCL2. Our study shows that targeting the cytokines IL-8 and MCP-1/CCL2 and associated signaling molecules may represent a promising therapeutic strategy in TN-IBC patients., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Inflammatory breast cancer (IBC) is a rare yet aggressive breast cancer variant, associated with a poor prognosis. The major challenge for IBC is misdiagnosis due to the lack of molecular biomarkers. We profiled dysregulated expression of microRNAs (miRNAs) in primary samples of IBC and non-IBC tumors using human breast cancer miRNA PCR array. We discovered that 28 miRNAs were dysregulated (10 were upregulated, while 18 were underexpressed) in IBC vs. non-IBC tumors. We identified 128 hub genes, which are putative targets of the differentially expressed miRNAs and modulate important cancer biological processes. Furthermore, our qPCR analysis independently verified a significantly upregulated expression of miR-181b-5p, whereas a significant downregulation of miR-200b-3p, miR-200c-3p, and miR-203a-3p was detected in IBC tumors. Receiver operating characteristic (ROC) curves implied that the four miRNAs individually had a diagnostic accuracy in discriminating patients with IBC from non-IBC and that miR-203a-3p had the highest diagnostic value with an AUC of 0.821. Interestingly, a combination of miR-181b-5p, miR-200b-3p, and miR-200c-3p robustly improved the diagnostic accuracy, with an area under the curve (AUC) of 0.897. Intriguingly, qPCR revealed that the expression of zinc finger E box-binding homeobox 2 ( ZEB2 ) mRNA, the putative target of miR-200b-3p, miR-200c-3p, and miR-203a-3p, was upregulated in IBC tumors. Overall, this study identified a set of miRNAs serving as potential biomarkers with diagnostic relevance for IBC.

Background: Childhood injuries are a significant and growing global public health problem, often with high morbidity and, at times, mortality. A large proportion of injuries in preschool children occur in or around the home. We aimed to identify socioeconomic and demographic factors associated with preschool children injuries in Egypt., Methods: Secondary data analysis were done for the Egyptian Demographic and Health Surveys (EDHS), 2014. Potential associated factors were measured from data on child welfare and questions on the prevalence of accidents and injuries of preschool children. These data were linked to the children demographic data, maternal age at marriage, working status of the mother, and questions on childcare arrangements., Results: Out of the 634 injured children, 520 (83.4%) children required medical care for their injuries. The most common reported injury was an open wound 288 (45.5%), followed by fractures 237 (35.7%), burns 124 (19.7%), electrical shock 12 (1.9%) and other unknown types of injury 15 (2.4%). There was a positive correlation between injury and child's age, household wealth, mother's age at marriage, and unsupervised children or children left in the care of a minor., Conclusion: Leaving children unsupervised or in the presence of other young children is significantly associated with the occurrence of child injuries.

Inflammatory breast cancer (IBC) is the most aggressive and lethal form of breast cancer, characterized by a high infiltration of tumor-associated macrophages and poor prognosis. To identify new biomarkers and to elucidate the molecular mechanisms underlying IBC pathogenesis, we investigated the expression pattern of heparanase (HPSE) and its activator cathepsin L (CTSL). First, we quantitated the HPSE and CTSL mRNA levels in a cohort of breast cancer patients after curative surgery (20 IBC and 20-non-IBC). We discovered that both HPSE and CTSL mRNA levels were significantly induced in IBC tissue vis-à-vis non-IBC patients ( p  <0 .05 and p  <0 .001, respectively). According to the molecular subtypes, HPSE mRNA levels were significantly higher in carcinoma tissues of triple negative (TN)-IBC as compared to TN-non-IBC ( p  <0 .05). Mechanistically, we discovered that pharmacological inhibition of HPSE activity resulted in a significant reduction of invasiveness in the IBC SUM149 cell line. Moreover, siRNA-mediated HPSE knockdown significantly downregulated the expression of the metastasis-related gene MMP2 and the cancer stem cell marker CD44. We also found that IBC tumors revealed robust heparanase immune-reactivity and CD163+ M2-type tumor-associated macrophages, with a positive correlation of both markers. Moreover, the secretome of axillary tributaries blood IBC CD14+ monocytes and the cytokine IL-10 significantly upregulated HPSE mRNA and protein expression in SUM149 cells. Intriguingly, massively elevated IL-10 mRNA expression with a trend of positive correlation with HPSE mRNA expression was detected in carcinoma tissue of IBC. Our findings highlight a possible role played by CD14+ monocytes and CD163+ M2-type tumor-associated macrophages in regulating HPSE expression possibly via IL-10. Overall, we suggest that heparanase, cathepsin L and CD14+ monocytes-derived IL-10 may play an important role in the pathogenesis of IBC and their targeting could have therapeutic implications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors.)

Background: We aimed to investigate the risk and survival of chronic myeloid leukemia (CML) after breast cancer (BC) diagnosis., Methods: We used the Surveillance, Epidemiology, and End Results 'SEER' database. Females, diagnosed with BC between 1992 and 2014, were selected and followed for the development of CML after a 6-month latency period from BC diagnosis. We used the Multiple Primary Standardized Incidence Ratios session of the SEER*Stat software (version 8.3.4) to calculate the Observed/Expected (O/E) ratios with 95% confidence intervals (CI). To calculate the overall survival, we performed an unadjusted Kaplan-Meier analysis using the SPSS software., Results: We included 474,866 females with BC, of which 178 were later diagnosed with CML. We found the risk of CML to increase significantly after BC diagnosis (O/E = 1.26, 95% CI: 1.08-1.45) and the risk was specifically higher within the first 5 years of diagnosis (O/E = 1.45, 95% CI: 1.16-1.8). When the risk was stratified by cancer stage, localized BC was associated with a significant increase in CML risk within 5 years of diagnosis (O/E = 1.4, 95% CI: 1.06-1.82), while regional BC was associated with a significant increase in CML risk after more than 5 years of diagnosis (O/E = 1.59, 95% CI: 1.09-2.25). Moreover, radiotherapy, chemotherapy, and presence of hormonal receptors were associated with a significant increase in CML risk in BC patients. The median overall survival of CML after BC was 28 months., Conclusion: Breast cancer patients have an increased risk of developing CML and further investigation is required to establish the causes of this finding., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Herein, we aimed to identify the immunomodulatory role of tumor Syndecan-1 (CD138) in the polarization of CD4+ T helper (Th) subsets isolated from the tumor microenvironment of inflammatory breast cancer (IBC) and non-IBC patients. Lymphocytes and mononuclear cells isolated from the axillary tributaries of non-IBC and IBC patients during modified radical mastectomy were either stimulated with the secretome as indirect co-culture or directly co-cultured with control and Syndecan-1-silenced SUM-149 IBC cells. In addition, peripheral blood mononuclear cells (PBMCs) of normal subjects were used for the direct co-culture. Employing flow cytometry, we analyzed the expression of the intracellular IFN-γ, IL-4, IL-17, and Foxp3 markers as readout for basal and co-cultured Th1, Th2, Th17, and Treg CD4+ subsets, respectively. Our data revealed that IBC displayed a lower basal frequency of Th1 and Th2 subsets than non-IBC. Syndecan-1-silenced SUM-149 cells significantly upregulated only Treg subset polarization of normal subjects relative to controls. However, Syndecan-1 silencing significantly enhanced the polarization of Th17 and Treg subsets of non-IBC under both direct and indirect conditions and induced only Th1 subset polarization under indirect conditions compared to control. Interestingly, qPCR revealed that there was a negative correlation between Syndecan-1 and each of IL-4, IL-17, and Foxp3 mRNA expression in carcinoma tissues of IBC and that the correlation was reversed in non-IBC. Mechanistically, Syndecan-1 knockdown in SUM-149 cells promoted Th17 cell expansion via upregulation of IL-23 and the Notch ligand DLL4. Overall, this study indicates a low frequency of the circulating antitumor Th1 subset in IBC and suggests that tumor Syndecan-1 silencing enhances ex vivo polarization of CD4+ Th17 and Treg cells of non-IBC, whereby Th17 polarization is possibly mediated via upregulation of IL-23 and DLL4. These findings suggest the immunoregulatory role of tumor Syndecan-1 expression in Th cell polarization that may have therapeutic implications for breast cancer., Competing Interests: The authors have declared that no competing interests exist.

We aimed to explore the efficacy of active caspase-3 and X-chromosome linked inhibitor of apoptosis protein (XIAP) as diagnostic markers for breast cancer. Furthermore, we examined the relationship between the examined parameters and clinicopathological factors. The current study involved 96 patients diagnosed with breast cancer and 40 patients had benign breast diseases. The expression of active caspase-3 was analyzed by both ELISA and Western blot, whereas the expression of XIAP was determined by ELISA in cell lysates. Active caspase-3 was significantly downregulated, while XIAP was markedly upregulated in patients with breast cancer in comparison to benign group. A significant negative correlation was observed between active caspase-3 and XIAP in breast cancer patients. Low active caspase-3 expression was associated with high grade, whereas, the high XIAP level was correlated with poorly differentiated tumors and late tumor stages. The sensitivity and specificity were 73.96% and 80.0% for active caspase-3, and, 70.83% and 82.5% for XIAP. A combination of active caspase-3 and XIAP provided a promising sensitivity of 88.54% and specificity of 90.0%. Our data indicate that active caspase-3 and XIAP could be substantial diagnostic markers for breast cancer patients.

Purpose: Plasmacytoid dendritic cells (PDCs) infiltration into breast cancer tissues is associated with poor prognosis. Also, CXCR4 shows compelling evidences to be exploited by cancer cells to migrate to distant sites. The present study investigated lymph node metastasis in the light of PDCs infiltration and the potential cross talk with CXCR4/SDF-1 chemokine axis., Methods: We assessed circulating PDCs proportions drained from the axillary tributaries, and the in situ expression of both CD303 and CXCR4 in breast cancer patients with positive lymph nodes (pLN) and negative lymph nodes (nLN) using immunohistochemistry and flow cytometry. We also analyzed the expression of SDF-1 in lymph nodes of pLN and nLN patients. We studied the effect of the secretome of PDCs of pLN and nLN patients on the expression of CXCR4 and activation of NF-κB in human breast cancer cell lines SKBR3 and MCF-7. TNF-α mRNA expression level in PDCs from both groups was determined by qPCR., Results: Our findings indicate increased infiltration of PDCs in breast cancer tissues of pLN patients than nLN patients, which correlates with CXCR4 + cells percentage. Interestingly, SDF-1 is highly immunostained in lymph nodes of pLN patients compared to nLN patients. Our in vitro experiments demonstrate an upregulation of NF-κB expression and CXCR4 cells upon stimulation with PDCs secretome of pLN patients than those of nLN patients. Also, PDCs isolated from pLN patients exhibited a higher TNF-α mRNA expression than nLN patients. Treatment of MCF-7 cell lines with TNF-α significantly upregulates CXCR4 expression., Conclusions: Our findings suggest a potential role for microenvironmental PDCs in breast cancer lymph node metastasis via CXCR4/SDF-1 axis.

The aim of the present study was to evaluate the expression levels of the aryl hydrocarbon receptor (AHR) and its target gene CYP1B1 and to correlate their expression with Wnt5a/b-β-catenin, the CD44 + /CD24 (-/low) cancer stem cell (CSC) subset and factors associated with poor prognosis in inflammatory breast cancer (IBC) and non-IBC patients. The methods of analysis used were quantitative real-time PCR, western blotting, immunohistochemistry and flow cytometry. Compared to non-IBC tissues, IBC tissues exhibited the overexpression of AHR and its target gene/protein CYP1B1. AHR and CYP1B1 mRNA levels were associated with the poor clinical prognosis markers tumour grade, lymphovascular invasion, cell proliferation and lymph node metastasis. Furthermore, AHR expression correlated with the expression of Wnt5a/b and β-catenin signalling molecules, and Wnt5a mRNA expression was downregulated in the SUM149 human IBC cell line and the MDA-MB-231 non-IBC cell line upon inhibition of AHR. AHR gene knockout (CRISPR-Cas9) inhibits CYP1B1 and Wnt5a expression in the IBC cell line. The CD44 + /CD24 (-/low) subset was significantly correlated with the expression of AHR, CYP1B1, Wnt5a/b and β-catenin in IBC tissues. The overexpression of AHR and its target CYP1B1 correlated with the expression of Wnt5a/b and β-catenin, CSCs, and poor clinical prognostic factors of IBC. Thus, targeting AHR and/or its downstream target molecules CYP1B1 and Wnt5a/b may represent a therapeutic approach for IBC.

Inflammatory breast cancer (IBC) has a poor prognosis because of the lack of specific biomarkers and its late diagnosis. An accurate and rapid diagnosis implemented early enough can significantly improve the disease outcome. Vibrational spectroscopy has proven to be useful for cell and tissue characterization based on the intrinsic molecular information. Here, we have applied infrared and Raman microspectroscopy and imaging to differentiate between non-IBC and IBC at both cell and tissue levels. Two human breast cancer cell lines (MDA-MB-231 and SUM-149), 20 breast cancer patients (10 non-IBC and 10 IBC), and 4 healthy volunteer biopsies were investigated. Fixed cells and tissues were analyzed by FTIR microspectroscopy and imaging, while live cells were studied by Raman microspectroscopy. Spectra were analyzed by hierarchical cluster analysis (HCA) and images by common k-means clustering algorithms. For both cell suspensions and single cells, FTIR spectroscopy showed sufficient high inter-group variability to delineate MDA-MB-231 and SUM-149 cell lines. Most significant differences were observed in the spectral regions of 1096-1108 and 1672-1692 cm-1. Analysis of live cells by Raman microspectroscopy gave also a good discrimination of these cell types. The most discriminant regions were 688-992, 1019-1114, 1217-1375 and 1516-1625 cm-1. Finally, k-means cluster analysis of FTIR images allowed delineating non-IBC from IBC tissues. This study demonstrates the potential of vibrational spectroscopy and imaging to discriminate between non-IBC and IBC at both cell and tissue levels.

National and international experts in inflammatory breast cancer (IBC) from high-volume centers treating IBC recently convened at the 10th Anniversary Conference of the Morgan Welch Inflammatory Breast Cancer Research Program at The University of Texas MD Anderson Cancer Center in Houston Texas. A consensus on the clinical management of patients with IBC was discussed, summarized, and subsequently reviewed. All participants at the conference (patients, advocates, researchers, trainees, and clinicians) were queried using the MDRing electronic survey on key management issues. A summary of the expert consensus and participant voting is presented. Bilateral breast and nodal evaluation, breast magnetic resonance imaging, positron emission tomography/computed tomography, and medical photographs were endorsed as optimal. Neoadjuvant systemic therapy, modified radical mastectomy and level I and II ipsilateral axillary node dissection, post-mastectomy radiotherapy, adjuvant targeted therapy and hormonal therapy as indicated, and delayed reconstruction were agreed-upon fundamental premises of standard non-protocol-based treatment for IBC. Consideration for local-regional therapy in de novo stage IV IBC was endorsed to provide local control whenever feasible. Variation across centers and special circumstances were discussed., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Pro-carboxypeptidase B2 (pro-CPB2) or thrombin-activatable fibrinolysis inhibitor (TAFI) is a glycoprotein encoded by the CPB2 gene and deregulated in several cancer types, including breast cancer. Thrombin binding to thrombomodulin (TM), encoded by THBD, is important for TAFI activation. CPB2 gene expression is influenced by genetic polymorphism and cytokines such as interleukin 10 (IL-10). Our previous results showed that tumor infiltrating monocytes/macrophages (CD14 + /CD16 + ) isolated from inflammatory breast cancer (IBC) patients' secrete high levels of IL-10. The aim of the present study is to test genetic polymorphism and expression of CPB2 in healthy breast tissues and carcinoma tissues of non-IBC and IBC patients. Furthermore, to investigate whether IL-10 modulates the expression of CPB2 and THBD in vivo and in-vitro. We tested CPB2 Thr325Ile polymorphism using restriction fragment length polymorphism, (RFLP) technique in healthy and carcinoma breast tissues. The mRNA expression of CPB2, THBD and IL10 were assessed by RT-qPCR. Infiltration of CD14 + cells was assessed by immunohistochemistry. In addition, we investigated the correlation between infiltration of CD14 + cells and expression of IL10 and CPB2. Furthermore, we correlated IL10 expression with the expression of both CPB2 and THBD in breast carcinoma tissues. Finally, we validated the role of recombinant IL-10 in regulating the expression of CPB2 and THBD using different breast cancer cell lines. Our results showed that CPB2 genotypes carrying the high-risk allele [Thr/Ile (CT) and Ile/Ile (TT)] were more frequent in both IBC and non-IBC patients compared to control group. CPB2 genotypes did not show any statistical correlation with CPB2 mRNA expression levels or patients' clinical pathological properties. Interestingly, CPB2 and IL10 expression were significantly higher and positively correlated with the incidence of CD14 + cells in carcinoma tissues of IBC as compared to non-IBC. On the other hand, THBD expression was significantly lower in IBC carcinoma versus non-IBC tissues. Based on molecular subtypes, CPB2 and IL10 expression were significantly higher in triple negative (TN) as compared to hormonal positive (HP) carcinoma tissues of IBC. Moreover, CPB2 expression was positively correlated with presence of lymphovascular invasion and the expression of IL10 in carcinoma tissues of IBC patients. Furthermore, recombinant human IL-10 stimulated CPB2 expression in SUM-149 (IBC cell line) but not in MDA-MB-231 (non-IBC cell line), while there was no significant effect THBD expression. In conclusion, carcinoma tissues of IBC patients are characterized by higher expression of CPB2 and lower expression of THBD. Moreover, CPB2 positively correlates with IL10 mRNA expression, incidence of CD14 + cells and lymphovascular invasion in IBC patients. IL-10 stimulated CPB2 expression in TN-IBC cell line suggests a relevant role of CPB2 in the aggressive phenotype of IBC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: This study's primary objective was to investigate the prevalence of physical and chemical restraint use in selected elderly hospitalized patients., Results: This study was conducted in April 2014 in four major acute care hospitals. Trained data collectors assessed the use of physical and chemical restraint among all admitted elderly patients. There were 287 elderly patients (median age 64 years, 46% women). 32 patients were restrained. The overall prevalence of restraints was 11.1%, with physical restraint use alone at 3.2% and chemical restraints use alone at 7.3%. Restraint use varied by hospital type, with the highest at the private hospital (22.9%) and the lowest at the two university hospitals (< 6%). In conclusion the prevalence of physical and chemical restraint use among admitted elderly patients in Egypt is comparable to that seen in developed countries. However, the use appears to vary widely by hospital type. The use of restraints in the elderly remains an important question considering the increasing number of elderly.

Interleukin-10 is involved in carcinogenesis by supporting tumor escape from the immune response. The aim of this study was to assess the single nucleotide polymorphisms, -1082A/G, -819T/C and -592A/C, in interleukin-10 gene promoter in inflammatory breast cancer compared to non-inflammatory breast cancer and association of these polymorphisms with interleukin-10 gene expression. We enrolled 105 breast cancer tissue (72 non-inflammatory breast cancer and 33 inflammatory breast cancer) patients and we determined the three studied single nucleotide polymorphisms in all samples by polymerase chain reaction restriction fragment length polymorphism and investigated their association with the disease and with various prognostic factors. In addition, we assessed the expression of interleukin-10 gene by real-time quantitative reverse transcription polymerase chain reaction and the correlation between studied single nucleotide polymorphisms and interleukin-10 messenger RNA expression. We found co-dominant effect as the best inheritance model (in the three studied single nucleotide polymorphisms in non-inflammatory breast cancer and inflammatory breast cancer samples), and we didn't identify any association between single nucleotide polymorphisms genotypes and breast cancer prognostic factors. However, GCC haplotype was found highly associated with inflammatory breast cancer risk (p < 0.001, odds ratio = 43.05). Moreover, the expression of interleukin-10 messenger RNA was significantly higher (p < 0.001) by 5.28-fold and 8.95-fold than non-inflammatory breast cancer and healthy control, respectively, where GCC haplotype significantly increased interleukin-10 gene expression (r = 0.9, p < 0.001).

The present study aimed to investigate the potential role of leptin in the progression of breast cancer and the associated cell proliferation signalling pathway(s). A total of 44 female patients diagnosed with breast cancer and 24 healthy donors from Ain Shams University Hospitals (Cairo, Egypt) were enrolled in the present study. The present study assessed leptin expression in breast cancer tissues at the gene and protein level using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry. The results demonstrate that the expression of leptin was significantly higher in tissue of breast cancer samples from obese patients than overweight and control samples (P<0.001). ELISA results indicated a significant increase (P<0.001) of leptin expression in obese patients. To investigate whether there is any difference in leptin expression between the peripheral and tumor microenvironment blood of patients with breast cancer, the concentration of leptin was assessed in plasma from both using ELISA assays. The results demonstrated a statistically significant increase in the level of leptin in plasma samples from the tumor microenvironment of obese patients with estrogen receptor positive (ER+) breast cancer, compared with peripheral plasma samples. Furthermore, the leptin gene was overexpressed in obese ER+ breast cancer tissue. RT-qPCR was also performed to assess the expression of genes involved in proliferation pathways including leptin receptor (LEPR), aromatase, mitogen activated protein kinase (MAPK) and signal transducer and activator of transcription-3 (STAT3). A positive association between leptin expression, LEPR, aromatase, MAPK and STAT3 was detected in tissue samples of patients with breast cancer. The current study concluded that leptin may enhance breast cancer progression by inducing the expression of JAK/STAT3, ERK1/2 and estrogen pathways in obese patients breast cancer.