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710 result(s) for "Ferrara, Francesco"
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Efficacy of synthetic glucocorticoids in COVID-19 endothelites
Since March 2020, the world has been fighting a global pandemic caused by a new coronavirus SARS-CoV-2 (COVID-19). SARS-CoV-2 is responsible for severe acute respiratory syndrome, an airway disease that can be severe and fatal in a percentage of cases. Patients with severe COVID-19 can develop extrapulmonary lesions, with renal, hepatic, cardiac, neurological, and tissue involvement that can cause further severe complications. On December 21, 2021, the European Medicines Agency (EMA) authorized the marketing of the first COVID-19 vaccine. However, several randomized trials are ongoing to find effective, safe, and widely available treatments. The most severe stages of COVID-19 infection are characterized by a multi-system inflammatory state induced by a cytokine storm causing multi-organ injury. Epidemiologic evidence has shown that glucocorticoids (GCs), particularly dexamethasone, are used in severe, hospitalized patients with COVID-19 with good therapeutic benefit. COVID-19 can also damage the endothelial system, causing microcirculatory disturbances and consequently leading to functional organ disorders. The combination of endothelial dysfunction with a generalized inflammatory state may contribute to the general pro-coagulative state described in patients with COVID-19 with increased risk of venous and arterial occlusions. The aim of this article is to describe the therapeutic utility of GCs in stabilizing the vascular endothelial barrier in COVID-19 infection. Indeed, we believe that the stabilization of the endothelial barrier and the anti-inflammatory effect of GCs could be the main effect underlying the therapeutic efficacy in COVID-19 patients.
Antifungal Drug Resistance: An Emergent Health Threat
Fungal infections, named mycosis, can cause severe invasive and systemic diseases that can even lead to death. In recent years, epidemiological data have recorded an increase in cases of severe fungal infections, caused mainly by a growing number of immunocompromised patients and the emergence of fungal pathogenic forms that are increasingly resistant to antimycotic drug treatments. Consequently, an increase in the incidence of mortality due to fungal infections has also been observed. Among the most drug-resistant fungal forms are those belonging to the Candida and Aspergillus spp. Some pathogens are widespread globally, while others are endemic in some areas only. In addition, some others may represent a health threat for some specific subpopulations and not for the general public. In contrast to the extensive therapeutic armamentarium available for the antimicrobial chemotherapeutic treatment of bacteria, for fungal infections there are only a few classes of antimycotic drugs on the market, such as polyenes, azoles, echinocandins, and a few molecules are under trial. In this review, we focused on the systemic mycosis, highlighted the antifungal drug compounds available in the pipeline, and analyzed the main molecular mechanisms for the development of antifungal resistance to give a comprehensive overview and increase awareness on this growing health threat.
Circulating Tumor Cells as Predictive and Prognostic Biomarkers in Solid Tumors
Circulating tumor cells (CTCs) have emerged as pivotal biomarkers with significant predictive and prognostic implications in solid tumors. Their presence in peripheral blood offers a non-invasive window into the dynamic landscape of cancer progression and treatment response. This narrative literature review synthesizes the current state of knowledge surrounding the multifaceted role of CTCs in predicting clinical outcomes and informing prognosis across a spectrum of solid tumor malignancies. This review delves into the evolving landscape of CTC-based research, emphasizing their potential as early indicators of disease recurrence, metastatic potential, and therapeutic resistance. Moreover, we have underscored the dynamic nature of CTCs and their implications for personalized medicine. A descriptive and critical analysis of CTC detection methodologies, their clinical relevance, and their associated challenges is also presented, with a focus on recent advancements and emerging technologies. Furthermore, we examine the integration of CTC-based liquid biopsies into clinical practice, highlighting their role in guiding treatment decisions, monitoring treatment efficacy, and facilitating precision oncology. This review highlights the transformative impact of CTCs as predictive and prognostic biomarkers in the management of solid tumors by promoting a deeper understanding of the clinical relevance of CTCs and their role in advancing the field of oncology.
Atopic dermatitis: treatment and innovations in immunotherapy
Atopic dermatitis (AD) is a common inflammatory skin disease characterized by itching and skin barrier dysfunction. Moderate to severe AD is often refractory to first-line topical treatments, and systemic immunosuppressants have been shown to be effective but have significant adverse effects. The paucity of basic treatments has contributed to the development of targeted topical and systemic immunotherapies based on the use of small molecules and biologic drugs which can directly interact with AD pathogenetic pathways. They represent a new era of therapeutic innovation. Additional new treatments are desirable since AD is a heterogeneous disease marked by different immunological phenotypes. This manuscript will review the mechanism of action, safety profile, and efficacy of promising new systemic immunological treatments for AD. Since moderate to severe AD can result in poor quality of life, the development of targeted and well-tolerated immunomodulators is a crucial purpose. The introduction of new pharmacological agents may offer new therapeutic options. However, there is the need to evaluate how \"narrow-acting\" agents, such as individual interleukin inhibitors, will perform under the safety and efficacy profiles compared with \"broad-acting\" agents, such as JAK inhibitors.
Lab-on-Chip for Exosomes and Microvesicles Detection and Characterization
Interest in extracellular vesicles and in particular microvesicles and exosomes, which are constitutively produced by cells, is on the rise for their huge potential as biomarkers in a high number of disorders and pathologies as they are considered as carriers of information among cells, as well as being responsible for the spreading of diseases. Current methods of analysis of microvesicles and exosomes do not fulfill the requirements for their in-depth investigation and the complete exploitation of their diagnostic and prognostic value. Lab-on-chip methods have the potential and capabilities to bridge this gap and the technology is mature enough to provide all the necessary steps for a completely automated analysis of extracellular vesicles in body fluids. In this paper we provide an overview of the biological role of extracellular vesicles, standard biochemical methods of analysis and their limits, and a survey of lab-on-chip methods that are able to meet the needs of a deeper exploitation of these biological entities to drive their use in common clinical practice.
Strong Prognostic Value of Microsatellite Instability in Intestinal Type Non-cardia Gastric Cancer
Background The clinical role of microsatellite instability (MSI) in gastric cancer (GC) is controversial. A large series of patients submitted to respective surgery for primary GC with a long follow-up time was evaluated. Methods 472 patients with prospectively collected frozen samples of normal mucosa and tumor tissue stored in a biological tissue bank were included. Microsatellite analysis was evaluated using 5 quasi monomorphic mononucleotide repeats (BAT-26, BAT-25, NR-24, NR-21, and NR-27). The presence of MSI in 2 or more loci was classified as MSI-H, whereas all other cases were included in the microsatellite-stable (MSS) group. Results MSI-H phenotype was found in 111 of 472 patients (23.5 %). MSI-H status was related significantly with older age, female gender, non-cardia location, WHO histotype, non-cardia Lauren intestinal type, and less advanced stages. Cancer-related 5-year survival was significantly higher in MSI-H versus MSS group (67.6 % vs. 35 %, p  < 0.001). Stratified analysis revealed a significant impact of MSI on prognosis in non-cardia tumors of intestinal type or tubular/poorly differentiated histology, particularly in stages II and III; multivariate Cox regression analysis confirmed MSS status as a strong predictor of poor prognosis (hazard ratio 2.65, 95 % CI 1.56–4.51, p  < 0.001) in non-cardia intestinal type. No prognostic value of MSI in the diffuse-mixed type and signet-ring cell/mucinous histotypes was observed. Conclusions MSI was confirmed as a significant predictor of long term outcome in a large series of GC with a long follow-up time, but the prognostic value is limited to selected histotypes of non-cardia tumors.
The risks of liver injury in COVID-19 patients and pharmacological management to reduce or prevent the damage induced
The global pandemic COVID-19 caused by the new coronavirus SARS-CoV-2 has already caused about 1.4 million deaths, and to date, there are no effective or direct antiviral vaccines. Some vaccines are in the last stages of testing. Overall mortality rates vary between countries, for example, from a minimum of 0.05% in Singapore to a maximum of 9.75 in Mexico; however, mortality and severity of COVID-19 are higher in the elderly and in those with comorbidities already present such as diabetes, hypertension, and heart disease. In this manuscript, we describe the clinical management aimed at preserving the liver or reducing the damage caused by COVID-19 and anti-COVID-19 drug treatments.
Renin Angiotensin System and Covid-19 Infection
Purpose The new coronavirus, called SARS-CoV-2, is responsible for the recent global pandemic COVID-19. The status of the global pandemic COVID-19 is currently underway, and the virus has caused about 1.11 million deaths. Several SARS-CoV-2 vaccines are in phase 3 clinical trials. Pending the availability of safe and effective vaccines, pharmacological treatments are experimental and aimed at avoiding the most serious complications of the infection. Methods This article explores and describes the scientific evidence in the literature and the scientific pharmacological and molecular rationale to consider drugs that modulate the RAS system as therapeutic agents that if administered appropriately can help the host organism to fight SARS-CoV-2 infection. Results It is known from the 2003 SARS epidemic that the critical receptor for SARS-CoV entry into host cells is the angiotensin 2 conversion enzyme (ACE2), the strain involved in the current SARS-CoV-2 epidemic is similar to the SARS-CoV strain involved in the 2002-2003 SARS epidemic. ACE-2 is part of the RAS system, the modulation of this enzyme could be of therapeutic efficacy. Conclusion Depending on pharmacological knowledge, and epidemiological evidence in the literature based on current knowledge of the mechanism of penetration of SARS-CoV-2 in cells, and the role of ACE-2 in the inflammatory state of infection, therapeutic treatments that modulate RAS could be a weapon to fight COVID-19 infection.