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Cancer remains a public concern and leading cause of death worldwide. Hepatocellular carcinoma, the most common form of liver cancer, is the third leading cause of cancer-related deaths. The number of cases is expected to double by 2040, according to GLOBOCAN 2020. Patients are usually diagnosed with advanced-stage HCC, which limits the number of effective treatment options. Oral-targeted therapies involving sorafenib and lenvatinib remain the first-line treatment option, which has recently been replaced by immunotherapy. Due to economic issues and ease of administration, the vast majority prefer oral systemic therapy. Sorafenib and lenvatinib, which belongs to tyrosine kinase inhibitors have few limitations of having large inter-individual variability in absorption, genetic polymorphisms, poor patient adherence to oral regimen limiting its long-term therapy. Therapeutic Drug Monitoring can overcome the limitations of TKIs and help individualise the dosage regimen with minimal adverse events. Therefore, this simple and rapid method using latest equipment enabled with ultra-high speed, high-sensitivity analysis (LCMS-8045) is expected to bring a change in clinical practice to improve the efficacy and safety of medication for optimal patient benefits.

IntroductionCoccidioidomycosis is a fungal infection endemic in the southwestern United States (US). Primary pulmonary coccidioidomycosis (PPC) is a leading cause of community-acquired pneumonia (CAP) in this region, although its diagnosis is often delayed, leading to lag in antifungal treatment and subsequent morbidity. The impact of early empiric antifungal therapy as part of treatment for CAP in endemic areas on clinical outcomes is unknown.MethodsPhase IV randomized, double-blind, placebo-controlled trial in individuals aged 18 years or older with CAP who met all eligibility criteria in Coccidioides endemic regions in the US. Eligible participants with CAP were randomized to receive either fluconazole (400 mg daily) or matching placebo for 42 days and were subsequently monitored for clinical resolution of their illness.ObjectivesThe primary objective was to assess the clinical response of early empiric antifungal therapy with fluconazole through Day 22 in subjects with PPC who were adherent to the study intervention. Secondary objectives included: assessments of the impact of early empiric antifungal therapy with fluconazole through Day 22 and 43 in subjects with PPC regardless of adherence, comparisons of the clinical response and its individual components over time by treatment group in subjects with PPC, assessments of days lost from work or school, hospitalization, and all-cause mortality.DiscussionThis trial was halted early due to slow enrollment (72 participants in one year, 33 received fluconazole and 39 received placebo). Of those enrolled, eight (11%) met the study definition of PPC. The study design and challenges are discussed.

Introduction: Coccidioidomycosis is a fungal infection endemic in the southwestern United States (US). Primary pulmonary coccidioidomycosis (PPC) is a leading cause of community-acquired pneumonia (CAP) in this region, although its diagnosis is often delayed, leading to lag in antifungal treatment and subsequent morbidity. The impact of early empiric antifungal therapy as part of treatment for CAP in endemic areas on clinical outcomes is unknown. Methods: Phase IV randomized, double-blind, placebo-controlled trial in individuals aged 18 years or older with CAP who met all eligibility criteria in Coccidioides endemic regions in the US. Eligible participants with CAP were randomized to receive either fluconazole (400 mg daily) or matching placebo for 42 days and were subsequently monitored for clinical resolution of their illness. Objectives: The primary objective was to assess the clinical response of early empiric antifungal therapy with fluconazole through Day 22 in subjects with PPC who were adherent to the study intervention. Secondary objectives included: assessments of the impact of early empiric antifungal therapy with fluconazole through Day 22 and 43 in subjects with PPC regardless of adherence, comparisons of the clinical response and its individual components over time by treatment group in subjects with PPC, assessments of days lost from work or school, hospitalization, and all-cause mortality. Discussion: This trial was halted early due to slow enrollment (72 participants in one year, 33 received fluconazole and 39 received placebo). Of those enrolled, eight (11%) met the study definition of PPC. The study design and challenges are discussed.

Neurological and psychiatric disorders occur in about 6 percent of the global population indicating a significant amount of people suffering from neurological disorder on a varying range in day to day life. On an extensive view, there is a critical requirement for the development of an alternative biomarker for these conditions. The thwart found in developing a biomarker is the difficulty in identifying a serum biomarker as these are mostly limited to the central nervous system (CNS). Serotonin being a neurotransmitter synthesized in the raphe nuclei of the brain could serve as an alternative biomarker. Here, the limitation is that it’s quickly metabolized by the mitochondrial enzyme MAO to 5-hydroxy indole acetic acid (5HIAA). This subsequent metabolite can be used for the analysis of serotonin levels in brain by analysing its concentration in the cerebrospinal fluid (CSF). Many theories suggest that the variations in serotonin level could lead to the development of many neurological and psychiatric disorders like Alzheimer’s disease (AD), schizophrenia, depression and so on. A decreased level is noticed in these patients but this could either be due to decreased production or increased reuptake of serotonin from the neuronal synapses. For instance, we know that a patient with depression shows a significant reduction in the levels of 5HIAA, due to the location of the raphe nuclei within regions of memory and cognition. Similarly, it does shows variation in AD and mild cognitive disorder. Evolving of 5HIAA as a biomarker, could be more delicate and enhanced strategy for monitoring these disorders.

Phospholipids of erythrocyte are found as bilayer with choline containing phospholipid like phosphatidyl choline and sphingomylein in the outer layer and amine containing phospholipid like phosphatidyl ethanolamine and phosphatidyl serine in the inner layer. This arrangement is known as phospholipid asymmetry. Lipid asymmetry is maintained throughout the entire life span of red blood cell and is disturbed when cells enter into the stage of apoptosis. We here discuss some of the conditions in which phospholipid asymmetry of erythrocyte is maintained and disturbed and the various detection methods to check the distortion phospholipid asymmetry of it. [ABSTRACT FROM AUTHOR]