Cancer stem cells (CSCs) are a rare cancer cell population, responsible for the facilitation, progression, and resistance of tumors to therapeutic interventions. This subset of cancer cells with stemness and tumorigenic properties is organized in niches within the tumor microenvironment (TME) and presents altered regulation in a variety of metabolic pathways, including glycolysis, oxidative phosphorylation (OXPHOS), as well as lipid, amino acid, and iron metabolism. CSCs exhibit similarities as well as differences when comparedto normal stem cells, but also possess the ability of metabolic plasticity. In this review, we summarize the metabolic characteristics of normal, non-cancerous stem cells and CSCs. We also highlight the significance and implications of interventions targeting CSC metabolism to potentially achieve more robust clinical responses in the future.

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS) that often progresses to severe disability. Previous studies have highlighted the role of T cells in disease pathophysiology; however, the success of B-cell-targeted therapies has led to an increased interest in how B cells contribute to disease immunopathology. In this review, we summarize evidence of B-cell involvement in MS disease mechanisms, starting with pathology and moving on to review aspects of B cell immunobiology potentially relevant to MS. We describe current theories of critical B cell contributions to the inflammatory CNS milieu in MS, namely (i) production of autoantibodies, (ii) antigen presentation, (iii) production of proinflammatory cytokines (bystander activation), and (iv) EBV involvement. In the second part of the review, we summarize medications that have targeted B cells in patients with MS and their current position in the therapeutic armamentarium based on clinical trials and real-world data. Covered therapeutic strategies include the targeting of surface molecules such as CD20 (rituximab, ocrelizumab, ofatumumab, ublituximab) and CD19 (inebilizumab), and molecules necessary for B-cell activation such as B cell activating factor (BAFF) (belimumab) and Bruton’s Tyrosine Kinase (BTK) (evobrutinib). We finally discuss the use of B-cell-targeted therapeutics in pregnancy.

According to the latest epidemiological data, breast cancer has recently been the most frequently diagnosed malignancy. To date, a body of evidence has established the involvement of multiple - and frequently interrelated - genetic and environmental factors in the pathogenesis of the disease. Emerging research on cancer prevention has highlighted the deterrence potential of interventions targeting environmental risk factors, particularly diet. In this aspect, the current review reveals the latest scientific results regarding epigallocatechin-3-gallate (EGCG) - a catechin most commonly found in green tea, as a potential chemopreventive dietary agent against breast cancer. in vitro studies on EGCG have demonstrated its effect on cell cycle progression and its potential to suppress several intracellular signaling pathways involved in breast cancer pathogenesis. In addition, EGCG possesses specific apoptosis-inducing characteristics that seem to enhance its role as a regulator of cell survival. Preclinical data seem to support using EGCG as an effective adjunct to EGFR-targeting treatments. The authors’ appraisal of the literature suggests that although preclinical evidence has documented the anticarcinogenic features of EGCG, limited large-scale epidemiological studies are investigating the consumption of EGCG - containing nutrients in the prevention and management of breast cancer risk. This literature review aims to liaise between preclinical and epidemiological research, surveying the existing evidence and unraveling relevant knowledge gaps.

Oral anticoagulation (OAC) is essential for preventing ischemic stroke events in patients with atrial fibrillation (AF), and leads to a significant ischemic prophylaxis, when appropriately used. However, there is still a risk of experiencing stroke events, despite being under anticoagulation. Stroke despite OAC is an increasingly common diagnosis, and pathophysiologically, it can be associated with several etiologies, ranging from AF competing mechanisms to true anticoagulation failure. While the cardioembolic origin of stroke is the most frequently identified etiology, other factors also have to be considered, as there is a significance risk of coexistence. This highlights the need for thorough diagnostic testing, evaluating each stroke etiology independently, with the use of imaging, biomarker and blood tests. Treating such patients, however, is more complex, as there is still uncertainty regarding the selection of OAC post-stroke, with data showing a superiority of direct OAC (DOAC), compared to vitamin K antagonists, in recurrent ischemic stroke prevention and conflicting results regarding OAC switch. Finally, the additive value of cardiac interventions, such as left atrial appendage occlusion (LAAO), in secondary prevention of stroke, is being explored, as it could potentially lead to significant stroke risk reduction. This review, therefore, provides an updated summary of the pathophysiology, diagnostics and therapeutics of stroke under OAC, while also discussing the future direction on the Achilles heel of AF management.

Transthyretin cardiac amyloidosis (ATTR) is prevalent among patients undergoing transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS). We aimed to develop and validate a risk score for predicting ATTR in this context. In the prospective multicentre GRECA-TAVI registry, 500 patients with severe AS scheduled for TAVI were screened for ATTR using technetium-99m-labeled DPD or PYP bone scintigraphy in 12 tertiary hospitals, from January 1st to December 31st, 2024. Clinical, echocardiographic, and electrocardiographic variables were recorded. A logistic regression-derived integer-based risk score was developed in a training cohort (n=350) and validated in a validation cohort (n=150). Model performance was evaluated using discrimination, calibration, and decision curve analyses. ATTR was diagnosed in 38 patients (7.6%). Five variables (age, sex, MWT, LVEF, and intracardiac device presence) formed the basis of an 8-point risk score. The score demonstrated good discrimination (AUC=0.75 training, 0.76 validation) and calibration (slope=1.15). A score ≥4 identified patients with a ∼16% ATTR prevalence compared to 2.4% in those with a score <4. This threshold captured most of the ATTR cases (73%) while recommending screening for only 36% of the cohort. Decision curve analysis showed net clinical benefit across clinically relevant thresholds (5-20%) over and above a guideline-recommended approach (based on MWT≥12mm) or a screen-all strategy. ATTR is common in patients with severe AS undergoing TAVI. A simple bedside score using routinely available variables effectively identifies those patients at risk for ATTR. Selective screening using this tool could improve diagnostic yield and resource allocation.

Background: Cardiac output (CO) estimation in patients in intensive care units (ICUs) by a non-invasive, automated, oscillometric, cuff-based apparatus (Mobil-O-Graph [MG]) is reproducible with acceptable accuracy versus thermodilution. In this pilot study, we tested the hypothesis that clinical decisions based on the MG device are in agreement with those based on invasive measurements using a Swan-Ganz catheter (SGC).Methods: Hemodynamic monitoring using an SGC and an MG was performed on 20 consenting critically ill patients in shock and under treatment, hospitalized in ICU. Retrospectively, three ICU physicians were asked to determine the need for blood transfusion, inotropes, fluids, diuretics, oxygen, and vasoconstrictive agents. Decisions (defined as “need for action” or “no action”) were based: (i) on SGC-acquired data and standard ICU monitoring (SIM); (ii) on MG-acquired data and SIM; (iii) SIM only. The decisions were compared using Cohen’s kappa agreement coefficient and Wilcoxon’s nonparametric test. Results: The overall number of decisions, as well as the subanalysis of “need for action” decisions, based either on information from an SGC or MG, were comparable. The significant positive kappa agreement coefficients indicated moderate to strong agreement. MG-derived decisions agreed with SGC-derived decisions to a significantly higher degree compared with SIM-based decisions.Conclusion: Clinical decisions in the ICU setting based on MG data were in acceptable agreement with SGC-based decisions. Larger studies are required to confirm this finding. MG devices may provide a simple, operator-independent, low-cost, first-line bedside method for simultaneous continuous monitoring of blood pressure and CO levels in critically ill patients outside the ICU.