49 research outputs found
FDA Adverse Event Reporting System Essentials: A Reflection on Study Conception
No full textNo abstract availabl
Overview of the Safety of Anti-VEGF Drugs: Analysis of the Italian Spontaneous Reporting System
No full textIntroduction: Anti-vascular endothelial growth factor (anti-VEGF) drugs are widely used for the treatment of several cancers and retinal diseases. The systemic use of anti-VEGF drugs has been associated with an increased risk of serious adverse reactions. Whether this risk is also related to intravitreal administration of anti-VEGF drugs is unclear. Objective: The aim of this study was to provide an overview of the safety of anti-VEGF drugs in oncology and ophthalmology settings using the Italian Spontaneous Reporting System (SRS). Methods: We selected all suspected adverse drug reaction (ADR) reports attributed to anti-VEGF drugs and conducted descriptive frequency analyses stratified by indication of use. As a measure of disproportionality, we calculated the proportional reporting ratio with 95% confidence intervals at the level of standardized Medical Dictionary for Regulatory Activities (MedDRA®) queries (SMQs). Results: Of a total of 2472 anti-VEGF drug-related reports, 2173 (87.9%) and 299 (12.1%) were attributed to systemic and intravitreal use of these drugs, respectively. The frequency of serious ADRs reported was higher for intravitreal administration of anti-VEGF drugs than for systemic use in patients with cancer (58.9 vs. 34.1%) (p < 0.001) and were disproportionally associated with ischemic heart disease and thromboembolic and cerebrovascular events. Most serious ADRs related to anti-VEGF drugs in patients with cancer are known and clinically relevant (e.g., gastrointestinal and vascular disorders). Conclusions: This study documented that serious ADRs and systemic toxicity may occur not only with systemic use of anti-VEGF drugs in patients with cancer but also with intravitreal administration. Close monitoring of cardio/cerebrovascular adverse events should be considered during treatment with all anti-VEGF drugs
Use of optical and acoustic instruments to study the turbid plumes generated by three different types of dredges during dredging activities inside and outside of a port
No full textAzithromycin in COVID-19 Patients: Pharmacological Mechanism, Clinical Evidence and Prescribing Guidelines
No full textThe global COVID-19 pandemic has led to a race to find medications that can improve the prognosis of the disease. Azithromycin, in association with hydroxychloroquine or chloroquine, has been proposed as one such medication. The aim of this review is to describe the pharmacological mechanism, clinical evidence and prescribing guidelines concerning azithromycin in COVID-19 patients. There is weak evidence on the antiviral and immunomodulating effects of azithromycin, which in addition is not based on results from COVID-19 patients specifically. Therefore, this antibacterial should be considered only as empirical treatment of community-acquired pneumonia (CAP), although not all current treatment guidelines are in agreement. After the initial expectations raised by a small trial, more recent evidence has raised serious safety concerns on the use of hydroxychloroquine or chloroquine with azithromycin to treat COVID-19 patients, as all these drugs have arrhythmogenic potential. The World Health Organization has not made recommendations suggesting the use of azithromycin with hydroxychloroquine or chloroquine as treatment for COVID-19, but some national organisations have taken a different position, recommending this as first-line treatment. Several scientific societies, including the American College of Cardiology, have cautioned about the risks of this treatment in view of the lack of evidence concerning its benefits
Psoriasis and psoriasiform reactions secondary to immune checkpoint inhibitors
No full textThe advent of Immune Checkpoint Inhibitors (ICIs) as a standard of care for several cancers, including melanoma and head/neck squamous cell carcinoma has changed the therapeutic approach to these conditions, drawing at the same time the attention on some safety issues related to their use. To assess the incidence of psoriasis as a specific immune-related cutaneous adverse event attributing to ICIs using the Eudravigilance reporting system. All reports of adverse drug reactions (ADRs) concerning either exacerbation of psoriasis or de novo onset of psoriasis/psoriasiform reactions associated to the use of Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) inhibitors ipilimumab and tremelimumab, and the Programmed cell Death protein 1/Programmed Death-Ligand 1 (PD-1/PD-L1) inhibitors nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, and cemiplimab were identified and extracted from the Eudravigilance reporting system, during the period between the date of market licensing (for each study drug) and 30 October 2020. 8213 reports of cutaneous ADRs associated with at least one of study drug have been recorded, of which 315 (3.8%) reporting psoriasis and/or psoriasiform reactions as ADR. In 70.8% of reports patients had pre-existing disease. ICIs-related skin toxicity is a well-established phenomenon, presenting with several conditions, sustained by an immune background based on the activity of some cells (CD4+/CD8+ T-cells, neutrophils, eosinophils, and plasmocytes), inflammatory mediators, chemokines, and tumor-specific antibodies. In this setting, psoriasis represents probably the most paradigmatic model of these reactions, thus requiring adequate recognition as no guidelines on management are now available
Differential effects of stromal derived factor-1a (SDF-1a) on early and late stages of human megakaryocytic development.
No full textStromal derived factor-1 alpha (SDF-1 alpha), the high-affinity ligand of CXC-chemokine receptor 4 (CXCR4), was added to human CD34(+) hematopoietic progenitor cells that can be induced to differentiate along the monocytic or megakaryocytic lineages. In control liquid cell cultures supplemented with two different cytokine cocktails: stem cell factor (SCF), interleukin-3 (IL-3), macrophage-colony stimulating factor (M-CSF), and 10% fetal calf serum (FCS), or, SCF and thrombopoietin (TPO), the expression of surface CXCR4 progressively increased in both the CD14(+) monocytic and CD41(+) megakaryocytic lineages. While SDF-1 alpha caused only modest effects on cells of the monocytic lineage, it induced profound down-regulation of CXCR4 in megakaryocytic cells at all stages of differentiation. Moreover, while SDF-1 alpha initially up-regulated the early megakaryocytic antigen CD41, at later time points (days 12-16) it induced down-regulation of the late megakaryocytic antigen CD42b. Consistently, at day 16, the number of mature megakaryocytes was significantly decreased in cultures supplemented with SDF-1 alpha. These findings indicate that, besides its primary role in regulating the retention of precursor cells in hematopoietic tissues, the SDF-1 alpha/CXCR4 system participates in the regulation of megakaryocytic development by stimulating the formation of immature megakaryoblasts and inhibiting the formation of mature megakaryocytes
Mathematical simulation of the suspended solids diffusion during dredging operations on the continental shelf off the coast of Lazio (Central Tyrrhenian Sea, Italy)
No full textArtificial nourishmentisapreferredstrategytoremedycoastalerosionalongasandycoast.Toconducta
pilot studyontheenvironmentalimpactoftheuseofsubmergedsandydepositstoartificially nourish
beaches, oceanographicandsedimentologicalstudieshavebeenperformedinpotentialdredgingsites
Post-Marketing Surveillance of CAR-T-Cell Therapies: Analysis of the FDA Adverse Event Reporting System (FAERS) Database
No full textINTRODUCTION: As chimeric antigen receptor T-cell therapies are becoming increasingly available in the armamentarium of the hematologist, there is an emerging need to monitor post-marketing safety. OBJECTIVE: We aimed to better characterize their safety profile by focusing on cytokine release syndrome and identifying emerging signals. METHODS: We queried the US Food and Drug Administration Adverse Event Reporting System (October 2017–September 2020) to analyze suspected adverse drug reactions to tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel). Disproportionality analyses (reporting odds ratio) were performed by comparing chimeric antigen receptor T-cell therapies with (a) all other drugs (reference group 1) and (b) other onco-hematological drugs with a similar indication, irrespective of age (reference group 2), or (c) restricted to adults (reference group 3). Notoriety was assessed through package inserts and risk management plans. Adverse drug reaction time to onset and cytokine release syndrome features were investigated. RESULTS: Overall, 3225 reports (1793 axi-cel; 1433 tisa-cel) were identified. The reported toxicities were mainly: cytokine release syndrome (52.2%), febrile disorders (27.7%), and neurotoxicity (27.2%). Cytokine release syndrome and neurotoxicity were often co-reported and 75% of the events occurred in the first 10 days. Disproportionalities confirmed known adverse drug reactions and showed unexpected associations: for example, axi-cel with cardiomyopathies (reporting odds ratio = 2.3; 95% confidence interval 1.2–4.4) and gastrointestinal perforations (2.9; 1.2–7.3), tisa-cel with hepatotoxicity (2.5; 1.1–5.7) and pupil disorders (15.3; 6–39.1). CONCLUSIONS: Our study confirms the well-known adverse drug reactions and detects potentially emerging safety issues specific for each chimeric antigen receptor T-cell therapy, also providing insights into a stronger role for tisa-cel in inducing some immunodeficiency-related events (e.g., hypogammaglobulinemia, infections) and coagulopathies, and for axi-cel in neurotoxicity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40264-022-01194-z
Supravital exposure to propidium iodide identifies apoptosis on adherent cells
No full text: Several studies indicate that plasma membrane changes during apoptosis are a general phenomenon. Among the flow cytometric methods to measure apoptosis, the Annexin V assay that detects the membrane exposure of phosphatidylserine (PS) is one of the most commonly used. However, the various treatments used for the detachment of adherent cells generally interfere with the binding of Annexin V to membrane PS, making apoptosis measurement a technical problem. Materials and Methods Apoptosis of different cell lines was investigated by fluorescence microscopy and multiple flow assays designed to assess loss of membrane integrity, translocation of PS, DNA fragmentation, and light scatter changes. Results and Conclusions We show that supravital propidium iodide (PI) assay stains adherent apoptotic cells, allowing flow cytometric quantification. Moreover, supravital exposure to PI without prior permeabilization identifies apoptotic cells as well as Annexin V and permits the simultaneous surface staining by FITC- and PE-conjugated monoclonal antibodies. As in the case of necrotic or permeabilized cells, fluorescence microscopy has revealed that PI staining of apoptotic cells is localized in the nucleus. This suggests that the binding of PI to the DNA/RNA structures is stable enough to withstand the trypsinization and/or washing procedures necessary to detach adherent cells
