Innovative Drug Modalities for the Treatment of Advanced Prostate Cancer.

Prostate cancer, a prevalent malignancy affecting the prostate gland, is a significant global health concern. Androgen-deprivation therapy (ADT) has proven effective in controlling advanced disease, with over 50% of patients surviving at the 10-year mark. However, a diverse spectrum of responses exists, and resistance to ADT may emerge over time. This underscores the need to explore innovative treatment strategies for effectively managing prostate cancer progression. Ongoing research endeavors persist in unraveling the complexity of prostate cancer and fostering the development of biologic and innovative approaches, including immunotherapies and targeted therapies. This review aims to provide a valuable synthesis of the dynamic landscape of emerging drug modalities in this context. Interestingly, the complexities posed by prostate cancer not only present a formidable challenge but also serve as a model and an opportunity for translational research and innovative therapies in the field of oncology.

The Impact of Antimicrobial Resistance in Cystic Fibrosis.

The phenomenon of antimicrobial resistance (AMR) is a critical global health challenge, with prospects indicating its potential to become the leading cause of death worldwide in the coming years. Individuals with pre-existing conditions, such as neoplastic disease undergoing chemotherapy, those on immunosuppressive therapy, and individuals with rare diseases like cystic fibrosis (CF), face heightened challenges due to AMR. CF is a rare disease caused by a deficiency in the synthesis of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channel protein, resulting in multi-organ clinical symptoms, particularly in the respiratory system. PwCF experience recurrent pulmonary exacerbations triggered by bacterial or viral infections, making them particularly vulnerable to the impact of AMR. This review delves into the complex relationship between AMR and climate dynamics, focusing on the unique challenges faced by individuals with CF. It discusses the methods employed to measure AMR, its global impact on antibiotic resistance, and the specific microbial communities present in the CF airway. The review also explores the intricacies of antimicrobial resistance within the context of cystic fibrosis, emphasizing the urgent need for research in this field.

The use of the biosimilar drug can lead to large health care savings that can be reinvested for continued innovation: Analysis of consumption of an Italian health care company.

BACKGROUND: Biosimilar drugs offer an opportunity for all global healthcare systems because they provide significant cost savings while ensuring equal efficacy and safety in the treatment of chronic diseases. These savings can be allocated to support ongoing innovation. METHODS: An analysis of the usage of major biosimilar drugs across various therapeutic areas has been conducted within an Italian healthcare company serving a population of over one million. Data on consumption, expenditure, and the number of treated patients has been extracted from the company's databases. Finally, a comparison with the year 2021 has been performed to determine if biosimilar drug usage increased in 2022. RESULTS: In 2022, the data reveals that a substantial portion of the analysed active ingredients are being used as biosimilar drugs, except in a few residual cases. However, among the most consumed drugs, resistance still exists in the case of Adalimumab and Etanercept, for which expenditure on originator drugs exceeds 2 million euros. CONCLUSION: The 2022-2021 comparison highlights the increasing use of biosimilar drugs. This data is encouraging and suggests that in the coming months, we may achieve total utilization, which would be to the benefit of the National Health System (NHS) and the citizens who can rely on an efficient and sustainable healthcare policy that is continually improving.

Intrahepatic cholangiocarcinoma biomarkers: Towards early detection and personalized pharmacological treatments.

Cholangiocarcinoma (CCA) is a rare malignancy originating from the biliary tree and is anatomically categorized as intrahepatic (iCCA), perihilar, and extrahepatic or distal. iCCA, the second most prevalent hepatobiliary cancer following hepatocellular carcinoma (HCC), constitutes 5-20 % of all liver malignancies, with an increasing incidence. The challenging nature of iCCA, combined with nonspecific symptoms, often leads to late diagnoses, resulting in unfavorable outcomes. The advanced phase of this neoplasm is difficult to treat with dismal results. Early diagnosis could significantly reduce mortality attributed to iCCA but remains an elusive goal. The identification of biomarkers specific to iCCA and their translation into clinical practice could facilitate diagnosis, monitor therapy response, and potentially reveal novel interventions and personalized medicine. In this review, we present the current landscape of biomarkers in each of these contexts. In addition to CA19.9, a widely recognized biomarker for iCCA, others such as A1BG, CYFRA 21-1, FAM19A5, MMP-7, RBAK, SSP411, TuM2-PK, WFA, etc., as well as circulating tumor DNA, RNA, cells, and exosomes, are under investigation. Advancing our knowledge and monitoring of biomarkers may enable us to improve diagnosis, prognostication, and apply treatments dynamically and in a more personalized manner.

Oligo-Metastatic Disease in Oncology: Exploring the Limits and the Potential of Genetic Assessment.

Oligo-metastatic disease (OMD) in the field of oncology denotes a distinct subset of metastatic tumors characterized by less aggressive biological behavior and extended survival times in comparison to their widely metastatic counterparts. While there is a general consensus regarding the existence of OMD, there remains a lack of widely accepted criteria for its a priori identification at the time of presentation. This review delves into the concept of OMD, placing a particular emphasis on the significance of understanding the limitations and potential of genetic assessments. It explores how these aspects are crucial in advancing our comprehension of this phenomenon. In a rapidly advancing era of precision medicine, understanding the intricacies of OMD opens up exciting possibilities for tailored treatment approaches. By elucidating the genetic underpinnings and dynamic nature of this condition, we stand to improve patient outcomes and potentially shift the paradigm of metastatic cancer management.

The impact of SARS-CoV-2 infection in patients with cystic fibrosis undergoing CFTR channel modulators treatment: a literature review.

Several risk factors for Coronavirus-2019 (COVID-19) disease have been highlighted in clinical evidence. Among the various risk factors are advanced age, metabolic illness such as diabetes, heart disease, and diseases of the respiratory system. Cystic Fibrosis (CF) is a rare disease with autosomal recessive transmission, characterised by a lack of synthesis of the CFTR channel protein, and multi-organ clinical symptoms mainly affecting the respiratory tract with recurrent pulmonary exacerbations. In view of the pathophysiological mechanisms, CF disease should be in theory considered a risk factor for SARS-CoV2 or severe COVID-19. However, recent clinical evidence seems to point in the opposite direction, suggesting that CF could be a protective factor against severe COVID-19. Possibly, the lack of presence or function of the CFTR channel protein could be linked to the expression of the membrane glycoprotein ACE-2, a key enzyme for the endocellular penetration of SARS-CoV-2 and related to the pathophysiology of COVID-19 disease. Furthermore, CFTR channel modulating agents could indirectly influence the expression of ACE-2, playing an important role in restoring the proper functioning of mucociliary clearance and the pulmonary microbiome in the host response to SARS-CoV-2 infection. In this review, the authors attempt to shed light on these important associations of issues that are not yet fully elucidated.

The Italian experience with the use of monitoring registers attached to negotiated agreements (MEAs) of the Italian Medicines Agency is a tool for governance and clinical appropriateness.

The use of monitoring registers with annexed negotiation agreements (MEAs) of the Italian Medicines Agency (AIFA) are the pillar of Italian healthcare governance to guarantee the correct allocation of economic healthcare resources. In Italy, an analysis was conducted in the context of a local health authority where all negotiation activities were implemented to verify the amount of reimbursements that can be recovered through the use of all available procedures on the monitoring registers. The purpose of this analysis was to highlight any criticalities which, if not properly addressed by doctors and pharmacists, can lead to considerable financial loss. Correct verification by the hospital pharmacy resulted in an economic recovery of approximately EUR 579,443.40 for the year 2022 and EUR 682,225.30 in the first 9 months of 2023. This analysis is intended to highlight how effective collaboration between doctors and pharmacists can lead to clear economic advantages with an efficient health system to the total benefit of citizens.

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.

Therapeutic and Unconventional Strategies to Contrast Antimicrobial Resistance: A Literature Review.

The fast emergence and spread of drug-resistant infectious pathogens and the resulting increase in associated and attributable deaths is a major health challenge globally. Misuse of antibiotics, insufficient infection prevention and control (IPC) in hospitals, food, animal feed, and environmental contamination due to drug-resistant microbes and genes have been the main drivers for antimicrobial resistance (AMR). AMR can lead to ineffective drug treatment, persistence of infection, and risk of severe disease especially in frail, immunocompromised, elderly patients. It is estimated that AMR will cause around 10 million deaths every year after 2050, the same number of deaths due to cancer occurring every year in present times. AMR affects the progress towards the Sustainable Development Goals (SDGs) and is crucial for pandemic preparedness and response. Therefore, the international authorities such as G7 and G20, the World Bank, the World Health Organization (WHO), the General Assembly of the United Nations, and the European Union call for innovative antibiotics and strategies to combat this health threat. To underline this emergency, two lists of resistant "priority pathogens" and a global research agenda for AMR in human health have been published by the WHO. Although investigation of safe and effective treatments remains a top priority, the pipeline for new antimicrobials is not promising, and alternative solutions are needed urgently. In recent times, the interest in fighting AMR has increased, and a number of preventive or therapeutic options have been explored. In this literature review, we discuss the scientific evidence and the limits of the main proven unconventional strategies to combat the AMR phenomenon in the human sector.

What Is the Role of Nutraceutical Products in Cancer Patients? A Systematic Review of Randomized Clinical Trials.

Chemotherapy represents the main pharmacological cancer treatment. Recently, positive effects emerged with the combination of anticancer therapy and nutraceutical products. The aim of this systematic review is to collect and synthesize the available scientific evidence regarding the potential effects of nutraceuticals on cancer cells. A systematic literature search of randomized clinical trials of nutraceutical products in patients with cancer published up to 15 December 2022 was conducted using three data sources: Embase, PubMed, and Web of Science. The effect of high-dose isoflavone supplements on prostate cancer resulted in stabilization or reduction of PSA concentrations in 50% of isoflavone group patients six months after treatment. High doses of vitamin D supplementation plus chemotherapy in patients with advanced or metastatic colorectal cancer showed a median PFS of 13.0 months (95% CI, 10.1-14.7 months) for 49 patients. The effect of vitamin D supplementation on markers of inflammatory level and antioxidant capacity in women with breast cancer showed a significant increase in serum vitamin D concentration (28 ± 2.6 to 39 ± 3.5; p = 0.004) after 8 weeks of treatment. In conclusion, nutraceutical supplements represent a potentially growing sector and can be utilized in medical treatment or nutrition to provide integrated medical care.

Time to treatment discontinuation in first-line non-small cell lung carcinoma: an overview.

OBJECTIVE: Time To Discontinuation (TTD) is defined as the time from the start of treatment to the end of treatment, usually occurring due to loss of efficacy or occurrence of adverse events. It has become an important surrogate efficacy endpoint especially in real-world studies due to its correlation with endpoints such as Progression Free Survival (PFS). The aim of the study is to conduct a literature review of all studies reporting TTD in first-line therapy of Non-Small Cell Lung Cancer (NSCLC). METHODS: All articles that reported TTD for any first-line treatment of NSCLC as of 30 June 2022 were extracted from the PubMed search engine. From these articles, the drugs, study type, and TTD values were extracted. A descriptive analysis of the studies was made, dividing the TTD by subgroup according to the type of treatment (traditional chemotherapy, target therapy, immunotherapy) and study design (clinical trials, real world studies). RESULTS: Fifty-five studies were considered for the analysis, of which 12 were published in 2021; 28 were clinical trials and 27 were real-world studies. Thirty of the studies considered involved conventional chemotherapy and expressed TTD values from 1.4 to 4.5 months, 5 of the studies considered involved immunotherapy with TTD values from 2.1 to 7.4 months and 18 of the studies considered target therapy, with TTD values from 4 to 31 months. The clinical trials reported TTD values from 1.4 to 16 months and the real-world studies from 2 to 31 months. CONCLUSION: Studies reporting TTD are increasing, most notably real-world studies. Given the increasing importance of TTD as an efficacy endpoint, it becomes critical to measure and monitor it in various therapeutic settings such as NSCLC. This is the first study to review all TTD values of drugs used in first-line NSCLC.

Safety and Effectiveness of Multiple Switching Between Originators and Biosimilars: Literature Review and Status Report on Interchangeability.

To date, numerous biosimilars are available in Europe and the practice of switching between originator and biosimilar or between two different biosimilars has become very widespread. However, multiple switching has not been adequately studied. The aim of this study is to conduct a literature review to assess the effectiveness and safety of multiple switches. All PubMed articles involving multiple switches from originator to biosimilars or between different biosimilars were considered. The relevant data on effectiveness and safety were extracted from these studies and the results were reported through descriptive analysis. Fifteen studies were considered, of which 11 were observational and 4 clinical trials. Inflammatory bowel disease and psoriasis were the most studied diseases. All studies reported that the effectiveness and safety in patients whose treatment involved multiple switches, was comparable to patients whose treatment involved a single or no switch at all. Some therapeutic fields such as oncology and renal insufficiency were not represented at all in the multiple switch studies. New evidence is desperately needed and should be made available to the scientific community and decision-makers.

Fatal hepatotoxicity due to sevoflurane use in a paediatric patient after aortic repair: reality or fiction? A case of pharmacovigilance.

Hepatotoxicity secondary to exposure of volatile anaesthetics is an exceptional finding, but its clinical interest depends on their frequent use, unpredictable appearance and potential severity. Halothane is the volatile anaesthetic most frequently involved in the development of liver dysfunction, especially after re-exposure. Sevoflurane has rarely been related to this life-threatening complication. We present the case of a 1-year-old girl who had undergone previous surgery for closure of a patent ductus arteriosus, and who developed severe acute hepatitis and died after undergoing surgical repair of an aortic isthmus narrowing by means of general anaesthesia with sevoflurane. Other possible causes of liver failure were excluded. This adverse event was classified as serious and was included in the national and European pharmacovigilance network, with the aim of preventing dangerous effects on patient health in clinical practice, by contributing to the enrichment of the literature.

Precision Medicine in the Treatment of Locally Advanced or Metastatic Urothelial Cancer: New Molecular Targets and Pharmacological Therapies.

Many variants of urothelial cancer present diagnostic challenges and carry clinical implications that influence prognosis and treatment decisions. The critical issues of treatment-resistant clones are a crucial barrier to care in individuals affected by urothelial carcinoma. Laying the foundations for the resistance evolution, a wide mutational heterogeneity characterizes urothelial carcinoma, noticeable also in patients affected by a early stage disease. In recent years the growing knowledge of the pathogenesis and molecular paths underlying the onset and progression of urothelial cancer are leading to the development of new therapies based on immune checkpoints. Chemotherapy and immunotherapy both operate selectively by shaping the developmental trajectory of urothelial carcinoma in the course of the illness. To date, a promising new therapeutic treatment is represented by antibody-drug conjugates, therapeutic tools that exploit the targeted ability of an antibody to administer cytotoxic drugs directly to the tumor. Indeed, nowadays in the clinical setting there are several treatments available for the treatment of locally advanced or metastatic urothelial cancer, from classic chemotherapeutics such as Gemcitabine, Cisplatin and Carboplatin, Paclitaxel and Docetaxel, to Programmed cell death protein 1 (PD-1) or Programmed death-ligand 1 (PD-L1) inhibitors such as Atezolizumab, Avelumab, Nivolumab, Pembrolizumab, up to anti-nectin 4 Enfortumab Vedotin and Sacituzumab govitecan, which binds Tumor-associated calcium signal transducer 2 (Trop-2) and activates as a topoisomerase inhibitor. The aim of this work is to describe the molecular mechanisms underlying the onset of the urothelial cancer and provide an overview of the immunotherapies that can be used in the clinical setting to counteract it, deepening the efficacy and safety results of the pivotal studies and the place in therapy of these treatments.

Nirmatrelvir-remdesivir association for non-hospitalized adults with COVID-19, point of view.

The efforts of the scientific world directed to identifying new antiviral drugs and therapies effective against SARS-CoV-2 continue. New oral antivirals against SARS-CoV-2 such as paxlovid have recently authorized. Evidence shows that these antivirals have good efficacy in reducing the risk of hospitalization in COVID-19 positive patients. Remdesivir is an authorized antiviral for the treatment of SARS-CoV-2 infection. To date, there are still few data in the literature on the safety profile and the risk of generating antiviral-resistant SARS-CoV-2 drug variants. In this manuscript we describe the evidence in the literature on the monotherapy use of paxlovid and monotherapy use of remdesivir, and the scientific hypothesis of using nirmatrelvir and remdesivir in association with the aim of increasing treatment efficacy, reducing the risk of adverse reactions and generating antiviral drug-resistant variants.