Systemic therapy for hepatocellular carcinoma (HCC): from bench to bedside

AbstractPrimary liver cancer is the fifth most common cancer worldwide and the third most common cause of cancer mortality. For patients with early resectable disease, surgical resection or transplantation is considered a potentially curative modality for hepatocellular carcinoma (HCC); on the other hand, for patients with unresectable or metastatic disease, treatment is essentially palliative and prior to the approval of sorafenib, there was no globally approved systemic treatment for patients presenting with unresectable or metastatic HCC. Sorafenib is the only systemic treatment to demonstrate a statistically significant but modest overall survival benefit in a large phase III trial. Thus, novel systemic approaches represent a high unmet medical need in advanced HCC. In this review article, we will try to take a journey through the history of systemic therapeutic options for HCC passing through the current standard options and exploring the potential new systemic options for this disease

Extended Cellular Automata Simulation Model For Fire Crowd Evacuation

In recent years, crowd evacuation in case of fire accidents has attracted considerate attention. Fire accidents occur in crowded buildings may cause heavy casualties. The study of fire crowd evacuation has become extremely necessary to minimize the loss of life and property. Large fires pose dangers; hence, computer simulations are conducted as alternative tools to the deficiencies in conducting actual fire evacuation experiments. Researchers have simulated evacuees’ movements in panic situations, such as fires, using the cellular automata (CA) model to predict and analyze evacuees’ behaviors during these panic situations. This could help minimize accidents and save lives. However, those researchers have either investigated fire accidents in a static scenario or propagate inaccurate fire circular fronts shape, such as the adoption of a square fire front shape. They have also applied a lot of constraints on the environmental and accident factors, such as fire location, fire spread speed, obstacles, which could show evacuees movements appeared unrealistic. In addition, the models used by those researchers ignored the effects of crowd pressure applied on evacuees around overcrowded exits during fire evacuation. In this research, the spiral fire movement technique was adopted using CA model to simulate the fire circular surface propagation shape, which presents a non-static fire-spreading behavior that able to estimate the average number of evacuees could be injured or killed by fire. In addition, the new extended CA parameters (fire spreading, congestion and path), the set of mathematics formulas, were introduced to simulate the decision-making of evacuees in terms of movements and judgments and their choices of actions

Relationship of vaccine efficacy to the kinetics of DC and T-cell responses induced by PLG-based cancer vaccines

Cancer vaccines are typically formulated for bolus injection and often produce short-lived immunostimulation resulting in poor temporal control over immune cell activation and weak oncolytic activity. One means of overcoming these limitations utilizes immunologically active biomaterial constructs. We previously reported that antigen-laden, macroporous PLG scaffolds induce potent dendritic cell (DC) and cytotoxic T-lymphocyte (CTL) responses via the controlled signaling of inflammatory cytokines, antigen and toll-like receptor agonists. In this study, we describe the kinetics of these responses and illustrate their fundamental relationship to potent tumor rejection when implanted subcutaneously in a mouse B16 model of melanoma. By explanting scaffolds from mice at times ranging from 1–7 d, a seamless relationship was observed between the production of controlled CTL responses, tumor growth and long-term survival in both prophylactic and therapeutic models. Scaffolds must be implanted for > 7 d to augment CTL responses via the prolonged presentation of tumor antigen, and the benefits included a notable regression of established tumors. Host DC infiltration into the porous material persisted for 12 days (peaking at day 5 ~1.4 x 106 cells), and a sharp attenuation in DC numbers coincided with peak CD8+ CTL infiltration at day 12 (~8 x 105 cells). Importantly, these PLG systems enhanced DC numbers in the draining lymph node, resulting in increased CD8(+) CTL subsets at days 10–16 of vaccination. These results indicate that material systems can finely control innate and adaptive immune cell responses to kill typically untreatable melanoma tumors and provide critical kinetic data for the design of vaccine carriers.Engineering and Applied Science

Productivity of 18F-FDG-PET/CT Diagnostic Tool in the Management of Pediatric Lymphoblastic Lymphoma

BACKGROUND: Lymphoblastic lymphoma (LL) comprises approximately 20% of childhood non-Hodgkin lymphoma (NHL); however, few studies had investigated the role of 18F-FDG-PET/CT in pediatric LL patients. We aim in this study to assess the role of 18F-FDG-PET/CT in the initial staging of newly diagnosed pediatric patients with LL as well as in the assessment of response after induction chemotherapy. PATIENTS AND METHODS: A prospective study enrolled biopsy proven newly diagnosed pediatric LL patients presenting in the Children Cancer Hospital Egypt (CCHE) during the period from October 2014 to October 2016. 18F-FDG-PET/CT was done initially before therapy and after induction chemotherapy in all patients. The patients were followed until the end of April 2018 (mean 23.5 months). RESULTS: All lymphoma involvement lesions (n = 43) were FDG avid and the intensity of nodal FDG uptake was variable. Two patients (11%) had bone marrow (BM) involvement by < 25% blast cells with corresponding positive BM focal uptake in 18F-FDG-PET/CT (SUVmax = 4 and 4.5). Evaluation post induction phase; CT detected 8 residual lesions in 8 patients (44.4%), while 18F-FDG-PET/CT detected only 3 Deauville-positive residual lesions in 3 patients (16.6%). No intensification of therapy was done in all post-induction positive patients. Repeated 18F-FDG-PET/CT at week 18 for post-induction patients revealed cleared all Deauville-positive residual lesions. On the other hand, repeated CT at week 18 detected regression but still residual in 4/8 (50%) post-induction CT lesions with clearance of the rest (50%). CONCLUSION: In initial staging, 18F-FDG-PET/CT is a useful tool for disease extent evaluation of pediatric LL. Moreover, it could provide a diagnostic hint for BM involvement. 18F-FDG-PET/CT done after induction therapy has a good negative predictive value with higher specificity than CT alone, but is not an indication for treatment intensification due to false positive results. However, larger sample size is required for better conclusion

Can Absence of Cardiac Activity on Point-of-Care Echocardiography Predict Death in Out-of-Hospital Cardiac Arrest?

AimThe purpose of this systematic review and meta-analysis was to evaluate the accuracy of the absence of cardiac motion on point-of-care echocardiography (PCE) in predicting termination of resuscitation (TOR), short-term death (STD), and long-term death (LTD), in adult patients with cardiac arrest of all etiologies in out-of-hospital and emergency department setting.MethodsA systematic review and meta-analysis was conducted based on PRISMA guidelines. A literature search in Medline, EMBASE, Cochrane, WHO registry, and ClinicalTrials.gov was performed from inspection to August 2022. Risk of bias was evaluated using QUADAS-2 tool. Meta-analysis was divided into medical cardiac arrest (MCA) and traumatic cardiac arrest (TCA). Sensitivity and specificity were calculated using bivariate random-effects, and heterogeneity was analyzed using I2 statistic.ResultsA total of 27 studies (3657 patients) were included in systematic review. There was a substantial variation in methodologies across the studies, with notable difference in inclusion criteria, PCE timing, and cardiac activity definition. In MCA (15 studies, 2239 patients), the absence of cardiac activity on PCE had a sensitivity of 72% [95% CI 62–80%] and specificity of 80% [95% CI 58–92%] to predict LTD. Although the low numbers of studies in TCA preluded meta-analysis, all patients who lacked cardiac activity on PCE eventually died.ConclusionsThe absence of cardiac motion on PCE for MCA predicts higher likelihood of death but does not have sufficient accuracy to be used as a stand-alone tool to terminate resuscitation. In TCA, the absence of cardiac activity is associated with 100% mortality rate, but low number of patients requires further studies to validate this finding. Future work would benefit from a standardized protocol for PCE timing and agreement on cardiac activity definition

EXPERIMENTAL CHARACTERISTICS OF RUBBERIZED CONCRETE

One of the construction industry’s main interest is using innovative materials to facilitate construction, extend service life, and minimize maintenance and rehabilitation costs. Recycling waste tire rubbers into conventional concrete materials constitutes one of the biggest challenging issues in modern concrete technology, which can significantly relieve critical environmental issues. However, the compressive strength reduction caused by the added rubber aggregates, albeit with significant ductility enhancement, has limited its application in concrete structures. The present study aimed at attaining the optimum ratio of crumb rubber ratio with minimal reduction in compressive strength to be used in large scale elements in which the ductility constitutes a critical design parameter. Different rubberized concrete mixes with different percentages of crumb rubber (CR) and different treatment were investigated. The main parameters were the type of crumb rubber (course or fine), the percentage of replacement (5%, 10%, 20%, and 30%), the treatment conditions (treated with NAOH, or without treatment), and using silica fume as partial replacement of cement. The test data were analyzed considering the workability, the compressive, tensile, and flexural strengths. The results revealed that the most appropriate concrete mix is using a 20% treated fine crumb rubber, with silica fume incorporation

Prediction of Axial Compressive Strength of Hybrid Reinforced Concrete Columns under Static Loading

Steel corrosion is thought to be one of the primary causes of the inadequate durability of concrete buildings in the maritime environment. Because of this, adopting Fiber-Reinforced Polymer (FRP) bars in harsh settings has attracted a lot of attention for its appealing mechanical properties as well as to prevent corrosion issues. But because there hasn't been much research in this area, we don't fully understand how fiber-reinforced polymer (FRP) bars behave when they are compressed. This work's goal is to assess the expected axial compressive strength of columns when hybrid reinforcement is used in place of steel reinforcement. Hybrid bars are steel bars surrounded by a cover shell of Glass or Carbon FRP (hybrid-steel) for longitudinal reinforcement and/or transverse reinforcement. 17 column specimens were included in an experimental study program that was created.The specimens were tested to failure with an axial loading condition. The parameters studied were the type of fibers, the percentage of steel in the hybrid reinforcement for longitudinal main reinforcement ρL(0.96, 0.44, and 0.25), the ratio of the web reinforcement (internal ties), the proportion of fiber in the hybrid bars, as well as the columns' cross sections' rectangularity. Based on the data, mathematical models were devised and assessed to forecast the load bearing capability of the column. The findings indicate that hybrid reinforced concrete columns have acceptable levels of dependability index in general

Klason Method: An Effective Method for Isolation of Lignin Fractions from Date Palm Biomass Waste

Klason lignin extraction method is one of the robust techniques for isolation of lignin from lignocellulosic palm biomass waste for future production of High Value Chemicals (HVCs). To elucidate the mechanism of hemicellulose and cellulose glycosidic bond distraction, lignocellulos