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Ashraf Omar,1 Ahmed Kaseb,2 Tamer Elbaz,1 Mohamed El-Kassas,3 Amr El Fouly,3 Abdel Fatah Hanno,4 Ahmed El Dorry,5 Ahmed Hosni,6 Amr Helmy,7 Amr S Saad,8 Ashwaq Alolayan,9 Basem Elsayed Eysa,10 Emad Hamada,11 Hamdy Azim,11 Hany Khattab,12 Hesham Elghazaly,8 Hesham Tawfik,13 Hisham Ayoub,14 Hussein Khaled,11 Ibtessam Saadeldin,11 Imam Waked,15 Eman MF Barakat,16 Mahmoud El Meteini,17 Mohamed Hamed Shaaban,6 Mohamed EzzElarab,10 Mohamed Fathy,17 Mohamed Shaker,5 Mohamed Sobhi,5 Mohamed Kamal Shaker,16 Mohamed ElGharib,5 Mohammed Abdullah,11 Mohesn Mokhtar,11 Mostafa Elshazli,18 Omar Mohamed Khaleil Heikal,14 Osama Hetta,5 Reda Mahmoud ElWakil,16 Sameh Abdel Wahab,5 Samir Shehata Eid,19 Yousri Rostom20 On behalf of the Egyptian Liver Cancer Committee Study Group1Department of Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt; 2Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA; 3Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt; 4Department of Gastroenterology, Faculty of Medicine, Alexandria University, Alexandria, Egypt; 5Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 6Department of Interventional Radiology, Faculty of Medicine, Cairo University, Cairo, Egypt; 7Department of Surgery, National Liver Institute Menoufia University, Menoufia, Egypt; 8Department of Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 9Department of Oncology, National Guard Hospital, Riyadh, Saudi Arabia; 10Department of Gastroenterology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt; 11Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt; 12Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt; 13Department of Oncology, Faculty of Medicine, Tanta University, Tanta Egypt; 14Department of Gastroenterology, Military Medical Academy, Cairo, Egypt; 15Department of Gastroenterology, Menoufia Liver Institute, Menoufia, Egypt; 16Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 17Department of Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 18Department of Surgery, Faculty of Medicine, Cairo University, Cairo, Egypt; 19Department of Oncology, Faculty of Medicine, Assiut University, Assiut, Egypt; 20Department of Oncology, Faculty of Medicine, Alexandria University, Alexandria, EgyptCorrespondence: Ashraf Omar, Department of Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt, Email abdelazizashraf@hotmail.comAbstract: Globally, hepatocellular carcinoma (HCC) is the fourth most common cause of death from cancer. The prevalence of this pathology, which has been on the rise in the last 30 years, has been predicted to continue increasing. HCC is the most common cause of cancer-related morbidity and mortality in Egypt and is also the most common cancer in males. Chronic liver diseases, including chronic hepatitis C, which is a primary health concern in Egypt, are considered major risk factors for HCC. However, HCC surveillance is recommended for patients with chronic hepatitis B virus (HBV) and liver cirrhosis; those above 40 with HBV but without cirrhosis; individuals with hepatitis D co-infection or a family history of HCC; and Nonalcoholic fatty liver disease (NAFLD) patients exhibiting significant fibrosis or cirrhosis. Several international guidelines aid physicians in the management of HCC. However, the availability and cost of diagnostic modalities and treatment options vary from one country to another. Therefore, the current guidelines aim to standardize the management of HCC in Egypt. The recommendations presented in this report represent the current management strategy at HCC treatment centers in Egypt. Recommendations were developed by an expert panel consisting of hepatologists, oncologists, gastroenterologists, surgeons, pathologists, and radiologists working under the umbrella of the Egyptian Society of Liver Cancer. The recommendations, which are based on the currently available local diagnostic aids and treatments in the country, include recommendations for future prospects.Keywords: hepatocellular carcinoma, clinical recommendations, Egyptian society of liver cancer, hepatitis c virus, Egypt, guidelines

Omer Mohamed, Hussein Elghazaly, Mohammed AllafFaculty of Medicine, Imperial College London, London, UKWe read with great interest the study by Zaeemzadeh et al1 regarding the evaluation of Physiology knowledge loss in medical students. In particular, their results that the extent of physiology knowledge loss was inversely correlated with time were fascinating, as this conflicts with the known relationship between the passing of time and memory loss,2 and also conflicts with similar studies.3,4 Furthermore, their findings contradict with our own experiences at Imperial College School of Medicine that time is a major contributor to knowledge loss.View the original paper by Zaeemzadeh and colleagues

Introduction: The BE-ALIVE score is an additive scoring system for estimating 30-day mortality in patients presenting with an acute coronary syndrome (ACS) [1]. However, it had only previously been tested on an internal validation cohort. The aim was to assess the scoring system on an external validation cohort., Methods: The scoring system comprises six domains: (1) Base Excess (1 point for < -2 mmols/L), (2) Age (<65 years: 0 points, 65-74: 1 point, 75-84: 2 points, ≥ 85: 3 points), (3) Lactate (<2 mmols/L: 0 points, 2-4.9: 1 point, 5-9.9: 3 points, ≥ 10: 6 points), (4) Intubated & Ventilated (2 points), (5) Left Ventricular function (normal or mildly impaired: -1 point, moderately impaired: 1 point, severely impaired: 3 points) and (6) External / out of hospital cardiac arrest (1 point). We applied the BE-ALIVE score was applied to 205 consecutive patients at a different institution., Results: Calibration was strong, with an observed to expected ratio of 1.01, a calibration slope of 1.26 and calibration in the large of -0.03. The Spiegelhalter's Z-statistic was -0.95 (p = 0.34). The AUC was 0.95 (0.92-0.98) in the external validation cohort versus 0.90 (0.85-0.95) during internal validation. Overall performance was excellent with a Brier score of 0.07 versus 0.06 during internal validation. The negative predictive value for 30-day mortality of a BE-ALIVE score < 4 was 98 %, with a positive predicted value of a score ≥ 10 of 95 %., Conclusions: The BE-ALIVE score remains a robust predictor of 30-day mortality in an external validation cohort., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

PIWI-interacting RNAs (piRNAs) have received a lot of attention for their functions in cancer research. This class of short non-coding RNAs (ncRNA) has roles in genomic stability, chromatin remodeling, messenger RNA (mRNA) integrity, and genome structure. We summarized the mechanisms underlying the biogenesis and regulatory molecular functions of piRNAs. Among all piRNAs studied in cancer, this review offers a comprehensive analysis of the emerging roles of piR-823 in various types of cancer, including colorectal, gastric, liver, breast, and renal cancers, as well as multiple myeloma. piR-823 has emerged as a crucial modulator of various cancer hallmarks through regulating multiple pathways. In the current review, we analyzed several databases and conducted an extensive literature search to explore the influence of piR-823 in carcinogenesis in addition to describing the potential application of piR-823 as prognostic and diagnostic markers as well as the therapeutic potential toward ncRNA precision., (© 2024. The Author(s).)

Background: The management of early breast cancer (BC) has witnessed an uprise in the use of neoadjuvant therapy and a remarkable reshaping of the systemic therapy postneoadjuvant treatment in the last few years, with the evolution of many controversial clinical situations that require consensus., Methods: During the 14th Breast-Gynecological and Immuno-Oncology International Cancer Conference held in Egypt in 2022, a panel of 44 BC experts from 13 countries voted on statements concerning debatable challenges in the neo/adjuvant treatment setting. The recommendations were subsequently updated based on the most recent data emerging. A modified Delphi approach was used to develop this consensus. A consensus was achieved when ≥75% of voters selected an answer., Results and Conclusions: The consensus recommendations addressed different escalation and de-escalation strategies in the setting of neoadjuvant therapy for early BC. The recommendations recapitulate the available clinical evidence and expert opinion to individualize patient management and optimize therapy outcomes. Consensus was reached in 63% of the statements (52/83), and the rationale behind each statement was clarified., (© 2024 American Cancer Society.)

Introduction: The aim of this systematic review was to identify the evidence in the literature for limb salvage with the introduction of duplex surveillance., Methods: A systematic review and meta-analysis was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA) methodology for all studies which compared a group undergoing clinical surveillance with a group undergoing combined clinical and duplex surveillance after endovascular therapy for peripheral arterial disease. MEDLINE, EMBASE, the Cochrane Database for Systematic Reviews, and ClinicalTrials.gov were searched for relevant studies by 2 reviewers. Studies were quality assessed using the ROBINS-I tool. An individual patient data survival analysis and meta-analysis for 1- and 2-year amputation outcomes using a random-effects model were performed., Results: Two low-quality nonrandomized studies met the inclusion criteria. There was a statistically and clinically significant reduction in major amputation in patients undergoing combined clinical and duplex surveillance (log-rank p<0.001). The number needed to treat to prevent 1 amputation at 2 years was 5 patients. At 1 year, the odds ratio (OR) for amputation was 0.22, 95% confidence interval (CI)=0.10-0.48, with no statistical heterogeneity. At 2 years, the numbers of patients were low and the effect on amputation was less certain OR=0.25, 95% CI=0.04-1.58., Conclusions: Preliminary, low-quality data suggests that there may be a clinically significant reduction in major amputation with the introduction of duplex surveillance. It is recommended that a randomized controlled trial is performed to confirm these findings and identify the anatomical subgroups that benefit the most from surveillance., Clinical Impact: "Two low-quality studies reveal a significant clinical impact: combined clinical and duplex surveillance markedly reduces major amputations (log-rank p<0.001). At 1-year, the odds ratio for amputation is 0.22 (95% CI=0.10-0.48), emphasizing limb salvage benefits. Despite less certainty at 2-years, a notable absolute risk reduction of 19% is seen, with a number needed to treat of 5. This underscores the urgent need for a randomized controlled trial to validate findings and identify key subgroups. The meta-analysis strongly advocates implementing duplex surveillance for a year post-endovascular interventions, especially in patients fit for reintervention, with important considerations for cost-effectiveness and focused clinical trials.", Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aims: To describe hypertension-related cardiovascular magnetic resonance (CMR) phenotypes in the UK Biobank considering variations across patient populations., Methods and Results: We studied 39 095 (51.5% women, mean age: 63.9 ± 7.7 years, 38.6% hypertensive) participants with CMR data available. Hypertension status was ascertained through health record linkage. Associations between hypertension and CMR metrics were estimated using multivariable linear regression adjusting for major vascular risk factors. Stratified analyses were performed by sex, ethnicity, time since hypertension diagnosis, and blood pressure (BP) control. Results are standardized beta coefficients, 95% confidence intervals, and P-values corrected for multiple testing. Hypertension was associated with concentric left ventricular (LV) hypertrophy (increased LV mass, wall thickness, concentricity index), poorer LV function (lower global function index, worse global longitudinal strain), larger left atrial (LA) volumes, lower LA ejection fraction, and lower aortic distensibility. Hypertension was linked to significantly lower myocardial native T1 and increased LV ejection fraction. Women had greater hypertension-related reduction in aortic compliance than men. The degree of hypertension-related LV hypertrophy was greatest in Black ethnicities. Increasing time since diagnosis of hypertension was linked to adverse remodelling. Hypertension-related remodelling was substantially attenuated in hypertensives with good BP control., Conclusion: Hypertension was associated with concentric LV hypertrophy, reduced LV function, dilated poorer functioning LA, and reduced aortic compliance. Whilst the overall pattern of remodelling was consistent across populations, women had greater hypertension-related reduction in aortic compliance and Black ethnicities showed the greatest LV mass increase. Importantly, adverse cardiovascular remodelling was markedly attenuated in hypertensives with good BP control., Competing Interests: Conflict of interest: S.E.P. provides consultancy to Cardiovascular Imaging Inc., Calgary, Alberta, Canada. The remaining authors have nothing to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

One of the key features of cancer is metabolic reprogramming that can be exploited to sensitize cancer cells to chemotherapy. Trimetazidine (TMZ) is a metabolic anti-ischemic drug that blocks the activity of long-chain 3-ketoacyl CoA thiolase leading to the inhibition of fatty acid oxidation., Aims: The objective of the current investigation was to evaluate the idea that TMZ could synergize the antitumor activity of doxorubicin (DOX)., Main Methods: The hypothesis was examined in vitro using the human breast cancer cell lines MCF-7 and MDA-MB231. In addition, the in vivo experiments were conducted using the Ehrlich solid phase carcinoma model., Key Findings: In vitro cytotoxicity experiments demonstrated that TMZ improved the potency of DOX in MCF-7 cell lines in a synergistic manner. In vivo testing confirmed that DOX/TMZ combination exhibits synergistic effect at both DOX/TMZ 1:10 and 1:5 ratios, where DOX was administered at one tenth and one fifth of its original dose, respectively. The co-treatment (1:5 ratio) significantly reduced tumor Nicotinamide adenine dinucleotide (NAD)+/NADH ratio (6.1-fold) and Adenosine triphosphate (ATP) levels (61 %) with concurrent activation of AMP-activated protein kinase (AMPK) (2.2-fold) and peroxisome proliferator-activated receptor-gamma coactivator (PGC)1-α (5.5-fold) protein expression versus control. The same treatment decreased the nuclear levels of NF-κB (p65) (57.5 %) and induced tumor apoptosis as evidenced by elevated Bax/Bcl-2 ratio (6.8-fold) along with active caspase-3 levels (6.6-fold) against control., Significance: The current investigation constitutes a proof-of-concept study that provided preclinical evidence for the anticancer activity of DOX/TMZ combination and warrants further investigation for repurposing TMZ in DOX protocols., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: Post-COVID-19 condition (PCC) is a complex heterogeneous disorder that has affected the lives of millions of people globally. Identification of potential risk factors to better understand who is at risk of developing PCC is important because it would allow for early and appropriate clinical support., Objective: To evaluate the demographic characteristics and comorbidities that have been found to be associated with an increased risk of developing PCC., Data Sources: Medline and Embase databases were systematically searched from inception to December 5, 2022., Study Selection: The meta-analysis included all published studies that investigated the risk factors and/or predictors of PCC in adult (≥18 years) patients., Data Extraction and Synthesis: Odds ratios (ORs) for each risk factor were pooled from the selected studies. For each potential risk factor, the random-effects model was used to compare the risk of developing PCC between individuals with and without the risk factor. Data analyses were performed from December 5, 2022, to February 10, 2023., Main Outcomes and Measures: The risk factors for PCC included patient age; sex; body mass index, calculated as weight in kilograms divided by height in meters squared; smoking status; comorbidities, including anxiety and/or depression, asthma, chronic kidney disease, chronic obstructive pulmonary disease, diabetes, immunosuppression, and ischemic heart disease; previous hospitalization or ICU (intensive care unit) admission with COVID-19; and previous vaccination against COVID-19., Results: The initial search yielded 5334 records of which 255 articles underwent full-text evaluation, which identified 41 articles and a total of 860 783 patients that were included. The findings of the meta-analysis showed that female sex (OR, 1.56; 95% CI, 1.41-1.73), age (OR, 1.21; 95% CI, 1.11-1.33), high BMI (OR, 1.15; 95% CI, 1.08-1.23), and smoking (OR, 1.10; 95% CI, 1.07-1.13) were associated with an increased risk of developing PCC. In addition, the presence of comorbidities and previous hospitalization or ICU admission were found to be associated with high risk of PCC (OR, 2.48; 95% CI, 1.97-3.13 and OR, 2.37; 95% CI, 2.18-2.56, respectively). Patients who had been vaccinated against COVID-19 with 2 doses had a significantly lower risk of developing PCC compared with patients who were not vaccinated (OR, 0.57; 95% CI, 0.43-0.76)., Conclusions and Relevance: This systematic review and meta-analysis demonstrated that certain demographic characteristics (eg, age and sex), comorbidities, and severe COVID-19 were associated with an increased risk of PCC, whereas vaccination had a protective role against developing PCC sequelae. These findings may enable a better understanding of who may develop PCC and provide additional evidence for the benefits of vaccination., Trial Registration: PROSPERO Identifier: CRD42022381002.

Introduction: Diabetic foot ulceration (DFU) is a common and challenging complication of diabetes. Risk stratification can guide further management. We aim to evaluate the prognostic performance of bedside tests used for peripheral arterial disease (PAD) diagnosis to predict DFU healing., Research Design and Methods: Testing for Arterial Disease in Diabetes (TrEAD) was a prospective observational study comparing the diagnostic performance of commonly used tests for PAD diagnosis. We performed a secondary analysis assessing whether these could predict DFU healing. Follow-up was performed prospectively for 12 months. The primary outcome was sensitivity for predicting ulcer healing. Secondary endpoints were specificity, predictive values, and likelihood ratios for ulcer healing., Results: 123 of TrEAD participants with DFU were included. In 12 months, 52.8% of ulcers healed. The best negative diagnostic likelihood ratio (NDLR) was observed for the podiatry ankle duplex scan (PAD-scan) monophasic or biphasic with adverse features(NDLR 0.35, 95% CI 0.14-0.90). The highest positive likelihood ratios were observed for toe brachial pressure index of ≤0.2 (positive diagnostic likelihood ratio (PDLR) 7.67, 95% CI 0.91-64.84) and transcutaneous pressure of oxygen of ≤20 mm Hg (PDLR 2.68, 95% CI 0.54-13.25). Cox proportional hazards modeling demonstrated significantly greater probabilities of healing with triphasic waveforms (HR=2.54, 95% CI 1.23-5.3, p=0.012) and biphasic waveforms with non-adverse features (HR=13.67, 95% CI 4.78-39.1, p<0.001) on PAD-scan., Conclusions: No single test performed well enough to be used in isolation as a prognostic marker for the prediction of DFU healing., Trial Registration Number: NCT04058626., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The incidence and mortality rates of ovarian cancer are increasing globally. Ovarian cancer is diagnosed at an advanced stage in 80% of women. After standard, platinum-based, front-line chemotherapy, poly (ADP-ribose) polymerase (PARP) inhibitors and antiangiogenic agents are successfully employed as maintenance strategies for newly diagnosed, advanced ovarian cancer patients. Landmark clinical studies, including SOLO-1, PAOLA-1, PRIMA, and VELIA, have provided crucial insights on optimizing first-line maintenance treatment using PARP inhibitors. A group of ovarian cancer experts, primarily from low- and middle-income countries, met in September 2019 to discuss new developments for the first-line treatment of ovarian cancer and its implications. Key implications of the evolving clinical data included: (1) olaparib or niraparib maintenance therapy appears to be the preferred choice for patients with BRCA 1/2 mutations; hence, BRCA testing is beneficial in identifying these patients; (2) niraparib monotherapy and olaparib in combination with bevacizumab have demonstrated significant benefit in progression-free survival (PFS) in homologous recombination deficiency (HRD)-positive patients; (3) bevacizumab, niraparib alone, or observation can be an alternative for HRD-negative patients; (4) further data is warranted to explore the role of PARP inhibitors in treating HRD-negative, ovarian cancer patients to confirm findings of the exploratory analysis of PRIMA; (5) PARP inhibitors may be beneficial for stage IV ovarian cancer patients with inoperable disease and patients with prior neoadjuvant chemotherapy; and (6) there is an urgent need to increase awareness in both clinicians and patients on BRCA and HRD testing for optimizing treatment decision-making and improving clinical outcomes in newly diagnosed, advanced ovarian cancer patients. In clinical medicine, the limited availability of family history (FH) information and the complexity of FH criteria has hampered the implementation of BRCA testing. Moreover, many cancer patients with BRCA mutations are not tested because they do not meet the criteria for FH. Consequently, BRCA testing in many high income countries, including the US and Australia, is underused and used inappropriately, which has resulted in the loss of valuable opportunities for better cancer management and cancer prevention., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jeffrey C.H. Goh – has been Advisory Board member, received sponsorship for conference and speaker’s bureau from AstraZeneca and Advisory Board Member for Tesaro. Charlie Gourley- has been part of advisory boards of Roche, Astrazeneca, MSD, Tesaro, Nucana, Clovis Foundation One, Sierra and has received research funding for Astrazeneca, Novartis, Aprea, Nucana and Tesaro. David SP Tan- has received research support from Astra Zeneca, Karyopharm Therapeutics, Bayer, Roche. Has been a part of Advisory Boards for Astra Zeneca, Roche, Bayer, MSD, Eisai, and Tessa Therapeutics and received honoraria from Astra Zeneca, Novartis, Roche, MSD, Bayer, Eisai, Takeda and Eisai. Angelica Nogueira-Rodrigues has been consultant for Eurofarma, Roche, Astra Zeneca, MSD, GSK and Eisai and received educational training from Roche, Eurofarma, Astra Zeneca, MSD. Hesham Elghazaly- No conflicts of interest. Marc Edy Pierre- No conflicts of interest. Gonzalo Giornelli- has been part of Adboard for AstraZeneca, Roche, MSD, Janssen Cilag and Speaker for AstraZeneca, MSD. Byoung-Gie Kim- No conflicts of interest. Flavia Morales – Vasquez- No conflicts of interest. Alexandra Tyulyandina- has received research support from Astra Zeneca, Roche, MSD and received honoraria from Astra Zeneca, Roche, MSD, Biocad, Tekeda, Pfiser, Eisai., (© 2022 The Authors.)

The SARS-CoV-2 pandemic has led to over 4.9 million deaths as of October 2021. One of the main challenges of creating vaccines, treatment, or diagnostic tools for the virus is its mutations and emerging variants. A couple of variants were declared as more virulent and infectious than others. Some approaches were used as nomenclature for SARS-CoV-2 variants and lineages. One of the most used is the Pangolin nomenclature. In our study, we enrolled 35 confirmed SARS-CoV-2 patients and sequenced the viral RNA in their samples. We also aimed to highlight the hallmark mutations in the most frequent lineage. We identified a seven-mutation signature for the SARS-CoV-2 C36 lineage, detected in 56 countries and an emerging lineage in Egypt. In addition, we identified one mutation which was highly negatively correlated with the lineage. On the other hand, we found no significant correlation between our clinical outcomes and the C36 lineage. In conclusion, the C36 lineage is an emerging SARS-CoV-2 variant that needs more investigation regarding its clinical outcomes compared to other strains. Our study paves the way for easier diagnosis of variants of concern using mutation signatures., 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 Agwa, Elghazaly, El Meteini, Yahia, Khaled, Abd Elsamee, Darwish, Elsayed, Hafez, Mahmoud, EM and Matboli.)

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in Egypt. A deep understanding of the molecular events occurring in HCC can facilitate the development of novel diagnostic and/or therapeutic approaches. In the present study, we describe a novel axis of hsa-circ-0000221 -miR-661-PTPN11 mRNA proposed by in silico and in vitro analysis and its role in HCC pathogenesis. We observe a reduction in the expression levels of hsa-circ-0000221 and PTPN11 mRNA in HCC patients' sera tested compared with control subjects. The reduction occurs with a concomitant increase in the expression of miR-661. Furthermore, the introduction of exogenous hsa-circ-0000221 into Hep-G2 or SNU449 cell lines results in detectable decrease in cellular viability and an increase in apoptotic manifestations that is associated with G1 accumulation and CCDN1 overexpression. Altogether, these findings indicate the tumor-suppressive role of hsa-circ-0000221 in HCC, which acts through miR-661 inhibition, along with a subsequent PTPN11 mRNA increase, where PTPN11 is known to inhibit cell proliferation in many forms of cancer. Our study encourages further investigation of the role of circRNAs in cancer and their potential use as molecular biomarkers.

(1) Background: The coronavirus (COVID-19) pandemic is still a major global health problem, despite the development of several vaccines and diagnostic assays. Moreover, the broad symptoms, from none to severe pneumonia, and the various responses to vaccines and the assays, make infection control challenging. Therefore, there is an urgent need to develop non-invasive biomarkers to quickly determine the infection severity. Circulating RNAs have been proven to be potential biomarkers for a variety of diseases, including infectious ones. This study aimed to develop a genetic network related to cytokines, with clinical validation for early infection severity prediction. (2) Methods: Extensive analyses of in silico data have established a novel IL11RA molecular network (IL11RNA mRNA, LncRNAs RP11-773H22.4 and hsa-miR-4257). We used different databases to confirm its validity. The differential expression within the retrieved network was clinically validated using quantitative RT-PCR, along with routine assessment diagnostic markers (CRP, LDH, D-dimmer, procalcitonin, Ferritin), in100 infected subjects (mild and severe cases) and 100 healthy volunteers. (3) Results: IL11RNA mRNA and LncRNA RP11-773H22.4, and the IL11RA protein, were significantly upregulated, and there was concomitant downregulation of hsa-miR-4257, in infected patients, compared to the healthy controls, in concordance with the infection severity. (4) Conclusion: The in-silico data and clinical validation led to the identification of a potential RNA/protein signature network for novel predictive biomarkers, which is in agreement with ferritin and procalcitonin for determination of COVID-19 severity.

In low-middle income countries (LMICs) and the Middle East and North Africa (MENA) region, there is an unmet need to establish and improve breast cancer (BC) awareness, early diagnosis and risk reduction programs. During the 12th Breast, Gynecological & Immuno-oncology International Cancer Conference - Egypt 2020, 26 experts from 7 countries worldwide voted to establish the first consensus for BC awareness, early detection and risk reduction in LMICs/MENA region. The panel advised that there is an extreme necessity for a well-developed BC data registries and prospective clinical studies that address alternative modalities/modified BC screening programs in areas of limited resources. The most important recommendations of the panel were: (a) BC awareness campaigns should be promoted to public and all adult age groups; (b) early detection programs should combine geographically distributed mammographic facilities with clinical breast examination (CBE); (c) breast awareness should be encouraged; and (d) intensive surveillance and chemoprevention strategies should be fostered for high-risk women. The panel defined some areas for future clinical research, which included the role of CBE and breast self-examination as an alternative to radiological screening in areas of limited resources, the interval and methodology of BC surveillance in women with increased risk of BC and the use of low dose tamoxifen in BC risk reduction. In LMICs/MENA region, BC awareness and early detection campaigns should take into consideration the specific disease criteria and the socioeconomic status of the target population. The statements with no consensus reached should serve as potential catalyst for future clinical research., (© 2021 UICC.)

Background: Acute coronary syndrome (ACS) is a major cause of death all over the world. STEMI represents a type of myocardial infarction with acute ST elevation. We aimed to assess the predictive power of potential RNA panel expression in acute coronary syndrome., Method: We used in silico data analysis to retrieve RNAs related to glycerophospholipid metabolism dysregulation and specific to ACS that results in the selection of Alpha/Beta hydrolase fold domain4 ( ABHD4 ) mRNA and its epigenetic regulators (Foxf1 adjacent noncoding developmental regulatory RNA ( FENDRR) lncRNA, miRNA-221, and miRNA-197 ). We assessed the expression of the serum RNA panel in 68 patients with ACS, 21 patients with chest pain due to non-cardiac causes, and 21 healthy volunteers by quantitative real-time polymerase chain reaction., Results: The study data showed significant down regulation in the expression of the serum levels of FENDRR lncRNA and miRNA-221-3p by 120-fold and 22-fold in Unstable angina (UA) in comparison with healthy volunteers, and by 8.6-fold and 2-fold in ST segment elevation myocardial infarction (STEMI) patients versus UA; concomitant upregulation in the expression of ABHD4 mRNA and miRNA-197-5p by 444-fold and 10-fold in UA compared with healthy volunteers, and by 1.54-fold and 4.5-fold in STEMI versus unstable angina. Performance characteristics analysis showed that the ABHD4 -regulating RNA panel were potential biomarkers for prediction of ACS. Moreover, there was a significant association between the 2 miRNAs and ABHD4 mRNA and the regulating FENDRR lncRNA., Conclusion: Collectively, ABHD4 mRNA regulating RNA panel based on putative interactions seems to be novel non-invasive biomarkers that could detect ACS early and stratify severity of the condition that could improve health outcome.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection provides a critical host-immunological challenge., Aim: We explore the effect of host-genetic variation in interferon-lambda-3 rs12979860, Tolloid Like-1 ( TLL1 ) rs17047200 and Discoidin domain receptor 1( DDR1 ) rs4618569 on host response to respiratory viral infections and disease severity that may probe the mechanistic approach of allelic variation in virus-induced inflammatory responses., Methods: 141 COVID-19 positive patients and 100 healthy controls were tested for interferon-lambda-3 rs12979860, TLL1 rs17047200 and DDR1 rs4618569 polymorphism by TaqMan probe-based genotyping. Different genotypes were assessed regarding the COVID-19 severity and prognosis., Results: There were statistically significant differences between the studied cases and control group with regard to the presence of comorbidities, total leucocytic count, lymphocytic count, CRP, serum LDH, ferritin and D-dimer ( p < 0.01). The CC genotype of rs12979860 cytokine, the AA genotype of TLL1 rs17047200 and the AA genotype of the rs4618569 variant of DDR1 showed a higher incidence of COVID-19 compared to the others. There were significant differences between the rs4618569 variant of DDR and the outcome of the disease, with the highest mortality in AG genotype 29 (60.4%) in comparison to 16 (33.3%) and 3 (6.2%) in the AA and GG genotypes, respectively ( p = 0.007*), suggesting that the A allele is associated with a poor outcome in the disease., Conclusion: Among people who carry C and A alleles of SNPs IFN-λ rs12979860 and TLL1 rs17047200, respectively, the AG genotype of the DDR1 rs4618569 variant is correlated with a COVID-19 poor outcome. In those patients, the use of anti- IFN-λ 3 , TLL1 and DDR1 therapy may be promising for personalized translational clinical practice.

Purpose: Advancements in the diagnosis and treatment of prostate cancer (PC) have rapidly progressed through the past years. Various factors should be taken into account while treating individual patients to ensure optimal and careful decision making. The purpose of this consensus review is to summarize the current practice patterns when managing patients with advanced prostate cancer (APC) as there is still a lack of or very limited evidence on its clinical management in some areas., Methods: Pre-defined questions were shared with experts prior to the consensus session that took place in Cairo, Egypt in April 2019 during the 8th International gastrointestinal, liver and uro-oncology conference (IGILUC). Voting was based mainly on the expert opinions of the panel after a thorough discussion and review of available evidence from guidelines or best evidence available concerning the topic at hand., Results: A strong consensus or unanimity was reached on 47% of the proposed questions. Notably, the panelists reached consensus on several topics based on high-level expert opinion. These findings contribute in several ways to our understanding of the management of PC and provide a basis for future recommendations. There was also a lack of consensus on other several topics, which suggests the need for further supporting data addressing these knowledge gaps., Conclusion: This review offers a thorough understanding of APC practice and offers insight on the various opinions shared amongst experts in the field that can serve as guidance regionally and deepens our understanding of disease management globally.

Background: Sorafenib was the first systemic therapy approved for the treatment of Child-Turcotte-Pugh (CTP) class A patients with advanced hepatocellular carcinoma (HCC). However, there are no biomarkers to predict survival and treatment outcomes and guide HCC systemic therapy. Type 1 insulin-like growth factor (IGF-1)/CTP composite score has emerged as a potential hepatic reserve assessment tool. Our study investigated the association of the IGF/CTP score with overall survival (OS) and progression-free survival (PFS) of HCC patients treated with sorafenib., Materials and Methods: In this prospective study, patients with HCC were treated with sorafenib and followed up until progression/death. We calculated the IGF/CTP score and used the Kaplan-Meier method and log-rank test to estimate and compare the time-to-event outcomes between patient subgroups., Results: 171 patients were included, 116 of whom were CTP class A. Median PFS for IGF/CTP score AA and AB patients were 6.88 and 4.28 months, respectively ( p = 0.1359). Median OS for IGF/CTP score AA and AB patients were 14.54 and 7.60 months, respectively ( p = 0.1378). The PFS and OS was superior in AA patients, but the difference was not significant, likely due to the sample size. However, there was a significant difference in early OS and PFS curves between AA and AB ( p = 0.0383 and p = 0.0099), respectively., Conclusions: In CTP class A patients, IGF/CTP score B was associated with shorter PFS and OS, however, study was underpowered to reach statistical significance. If validated in larger cohorts, IGF/CTP score may serve as stratification tool in clinical trials, a hepatic reserve assessment tool for HCC outcomes prediction and to assist in therapy decisions., Competing Interests: CONFLICTS OF INTEREST All authors report no commercial associations (e.g., consultancies, stock ownership, equity interests, or patent-licensing arrangements) that might pose a conflict of interest in connection with the submitted article., (Copyright: © 2021 Mohamed et al.)

Favipiravir is considered a potential treatment for COVID-19 due its efficacy against different viral infections. We aimed to explore the safety and efficacy of favipiravir in treatment of COVID-19 mild and moderate cases. It was randomized-controlled open-label interventional phase 3 clinical trial [NCT04349241]. 100 patients were recruited from 18th April till 18th May. 50 patients received favipiravir 3200 mg at day 1 followed by 600 mg twice (day 2-day 10). 50 patients received hydroxychloroquine 800 mg at day 1 followed by 200 mg twice (day 2-10) and oral oseltamivir 75 mg/12 h/day for 10 days. Patients were enrolled from Ain Shams University Hospital and Assiut University Hospital. Both arms were comparable as regards demographic characteristics and comorbidities. The average onset of SARS-CoV-2 PCR negativity was 8.1 and 8.3 days in HCQ-arm and favipiravir-arm respectively. 55.1% of those on HCQ-arm turned PCR negative at/or before 7th day from diagnosis compared to 48% in favipiravir-arm (p = 0.7). 4 patients in FVP arm developed transient transaminitis on the other hand heartburn and nausea were reported in about 20 patients in HCQ-arm. Only one patient in HCQ-arm died after developing acute myocarditis resulted in acute heart failure. Favipiravir is a safe effective alternative for hydroxychloroquine in mild or moderate COVID-19 infected patients.

Background: Cardiovascular disease (CVD) is the leading cause of death worldwide. Lifestyle changes are at the forefront of preventing the disease. This includes advice such as increasing physical activity and having a healthy balanced diet to reduce risk factors. Intermittent fasting (IF) is a popular dietary plan involving restricting caloric intake to certain days in the week such as alternate day fasting and periodic fasting, and restricting intake to a number of hours in a given day, otherwise known as time-restricted feeding. IF is being researched for its benefits and many randomised controlled trials have looked at its benefits in preventing CVD., Objectives: To determine the role of IF in preventing and reducing the risk of CVD in people with or without prior documented CVD., Search Methods: We conducted our search on 12 December 2019; we searched CENTRAL, MEDLINE and Embase. We also searched three trials registers and searched the reference lists of included papers. Systematic reviews were also viewed for additional studies. There was no language restriction applied., Selection Criteria: We included randomised controlled trials comparing IF to ad libitum feeding (eating at any time with no specific caloric restriction) or continuous energy restriction (CER). Participants had to be over the age of 18 and included those with and without cardiometabolic risk factors. Intermittent fasting was categorised into alternate-day fasting, modified alternate-day fasting, periodic fasting and time-restricted feeding., Data Collection and Analysis: Five review authors independently selected studies for inclusion and extraction. Primary outcomes included all-cause mortality, cardiovascular mortality, stroke, myocardial infarction, and heart failure. Secondary outcomes include the absolute change in body weight, and glucose. Furthermore, side effects such as headaches and changes to the quality of life were also noted. For continuous data, pooled mean differences (MD) (with 95% confidence intervals (CIs)) were calculated. We contacted trial authors to obtain missing data. We used GRADE to assess the certainty of the evidence.  MAIN RESULTS: Our search yielded 39,165 records after the removal of duplicates. From this, 26 studies met our criteria, and 18 were included in the pooled analysis. The 18 studies included 1125 participants and observed outcomes ranging from four weeks to six months. No studies included data on all-cause mortality, cardiovascular mortality, stroke, myocardial infarction, and heart failure at any point during follow-up. Of quantitatively analysed data, seven studies compared IF with ab libitum feeding, eight studies compared IF with CER, and three studies compared IF with both ad libitum feeding and CER. Outcomes were reported at short term (≤ 3 months) and medium term (> 3 months to 12 months) follow-up. Body weight was reduced with IF compared to ad libitum feeding in the short term (MD -2.88 kg, 95% CI -3.96 to -1.80; 224 participants; 7 studies; low-certainty evidence). We are uncertain of the effect of IF when compared to CER in the short term (MD -0.88 kg, 95% CI -1.76 to 0.00; 719 participants; 10 studies; very low-certainty evidence) and there may be no effect in the medium term (MD -0.56 kg, 95% CI -1.68 to 0.56; 279 participants; 4 studies; low-certainty evidence). We are uncertain about the effect of IF on glucose when compared to ad libitum feeding in the short term (MD -0.03 mmol/L, 95% CI -0.26 to 0.19; 95 participants; 3 studies; very-low-certainty of evidence) and when compared to CER  in the short term: MD -0.02 mmol/L, 95% CI -0.16 to 0.12; 582 participants; 9 studies; very low-certainty; medium term: MD 0.01, 95% CI -0.10 to 0.11; 279 participants; 4 studies; low-certainty evidence). The changes in body weight and glucose were not deemed to be clinically significant. Four studies reported data on side effects, with some participants complaining of mild headaches. One study reported on the quality of life using the RAND SF-36 score. There was a modest increase in the physical component summary score., Authors' Conclusions: Intermittent fasting was seen to be superior to ad libitum feeding in reducing weight. However, this was not clinically significant. There was no significant clinical difference between IF and CER in improving cardiometabolic risk factors to reduce the risk of CVD. Further research is needed to understand the safety and risk-benefit analysis of IF in specific patient groups (e.g. patients with diabetes or eating disorders) as well as the effect on longer-term outcomes such as all-cause mortality and myocardial infarction., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Purpose: There is much debate regarding the use of anticoagulation following vascular trauma. The aim of this meta-analysis was to compare the outcome of trauma following administration of anticoagulation medication., Methods: The literature search was carried out using Ovid MEDLINE and PubMed databases to search for keywords and MeSH terms including "Anticoagulation", "Vascular Surgery", "Vascular Trauma", "Vascular Repair", "Repair" and "Wounds and Injuries"., Results: Use of anticoagulation was associated with a better prognosis for overall vascular trauma outcomes (weighted OR 0.46; 95% CI 0.34-0.64; P < 0.00001), as well as reduced risk of amputation for both lower and upper limb vascular trauma (weighted OR 0.42; 95% CI 0.22-0.78; P = 0.007), and reduced occurrence of reoperation events and amputations in isolated lower limb vascular trauma (weighted OR 0.27; 95% CI 0.14-0.52; P < 0.0001)., Conclusion: There was a statistically significant correlation between the use of anticoagulation and vascular trauma outcome. A major limitation with many of the studies includes a lack of prospective analysis and therefore we recommend prospective studies to properly elucidate prognostic outcomes following use of these anticoagulants. Further studies need to be conducted to assess the effects of timing of anticoagulant delivery, dosages and severity of traumatic injury. Thus, this would prove to be very useful in the formation of guidelines.

Breast cancer is the most common malignancy among women worldwide. The current COVID-19 pandemic represents an unprecedented challenge leading to care disruption, which is more severe in low- and middle-income countries (LMIC) due to existing economic obstacles. This review presents the global perspective and preparedness plans for breast cancer continuum of care amid the COVID-19 outbreak and discusses challenges faced by LMIC in implementing these strategies. Prioritization and triage of breast cancer patients in a multidisciplinary team setting are of paramount importance. Deescalation of systemic and radiation therapy can be utilized safely in selected clinical scenarios. The presence of a framework and resource-adapted recommendations exploiting available evidence-based data with judicious personalized use of current resources is essential for breast cancer care in LMIC during the COVID-19 pandemic.

Purpose: To evaluate the efficacy and safety of an all-oral vinorelbine and capecitabine combination therapy in anthracycline- ± taxane-pretreated HER2/Neu-negative metastatic breast cancer (MBC)., Methods: A phase 2 trial including women >18 years with HER2/Neu-negative MBC previously exposed to anthracycline- ± taxane-based chemotherapy in the adjuvant or neoadjuvant setting. Enrolled patients received oral vinorelbine 60 mg/m(2) on days 1 and 8 and oral capecitabine 1,000 mg/m(2) twice daily on days 1-14 on a 3 weekly schedule. Patients with progressive disease after 3 cycles discontinued the study, while the remaining patients continued treatment for a maximum of 6 cycles., Results: From January 2007 to March 2011, 30 patients were enrolled in this study (median age 47 years). In the 28 evaluable patients, the overall response rate was 57.1 % (95 % CI 30-67 %), including 3 complete (10.7 %) and 13 partial (46.4 %) responses. Six (21.4 %) patients suffered from disease progression. With a median follow-up time of 13 months, the median time to disease progression was 8.6 months (95 % CI 6.2-10.6 months) and the median survival time was 27.2 months. Treatment-related adverse events were manageable, and no World Health Organization grade 4 toxicities were noted. Neutropenia observed in 6 (21.4 %) patients was the main grade 3 toxicity. Grade 3 nausea and vomiting were reported in 2 (7.1 %) and 3 (10.7 %) patients, respectively. Two (7.1 %) patients developed grade 3 hand and foot syndrome., Conclusion: These results show that the combination of oral vinorelbine and capecitabine is an effective and well-tolerated first-line regimen for HER2/Neu-negative MBC patients pretreated with anthracyclines ± taxanes.