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Topic Review
Ocular Side Effects of Immune Checkpoint Inhibitors
In the diverse arsenal of therapeutic tools against cancer, immune checkpoint inhibitors (ICI) have emerged as a new beacon of hope. By inhibiting the immune response’s “OFF” signal, ICIs activate the body’s immune system to attack cancerous growths. Eight immune checkpoint inhibitors have been approved by the FDA for their proven efficacy against multiple cancer types. Per their mechanism of action, ICIs produce a series of well-documented side effects secondary to the induction of immune activation commonly referred to as “immune-related adverse events” (IRAEs). These can affect any organ system, including the eye. Although rare, ocular IRAEs can have debilitating effects on patients’ quality of life and be sight-threatening.
  • 92
  • 17 Feb 2024
Topic Review
Ivacaftor (VX-770)
Ivacaftor possesses a molecular structure characterized by the presence of an N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydro-quinoline-3-carboxamide moiety. The quinolone scaffold within its composition is a crucial pharmacophore, significantly influencing drug discovery. This scaffold holds prominence as one of the primary classes of nitrogen-containing heterocycles found in various biologically active compounds and blockbuster drugs, as highlighted in the literature. The amide group serves as a crucial link between the “privileged building block” and the di-tert-butylphenol in ivacaftor’s structure. This linkage is of considerable importance in medicinal chemistry due to its multifaceted role.
  • 275
  • 17 Feb 2024
Topic Review
Gastric Outlet Obstruction Management
Gastric outlet obstruction (GOO) poses a common and challenging clinical scenario, characterized by mechanical blockage in the pylorus, distal stomach, or duodenum, resulting in symptoms such as nausea, vomiting, abdominal pain, and early satiety. Its diverse etiology encompasses both benign and malignant disorders. The spectrum of treatment modalities extends from conservative approaches to more invasive interventions, incorporating procedures like surgical gastroenterostomy (SGE), self-expandable metallic stents (SEMSs) placement, and the advanced technique of endoscopic ultrasound-guided gastroenterostomy (EUS-GE). While surgery is favored for longer life expectancy, stents are preferred in malignant gastric outlet stenosis. The novel EUS-GE technique, employing a lumen-apposing self-expandable metal stent (LAMS), combines the immediate efficacy of stents with the enduring benefits of gastroenterostomy. 
  • 283
  • 17 Feb 2024
Topic Review
Biomaterial-Based Responsive Nanomedicines for Targeting Solid Tumor Microenvironments
Solid tumors are composed of a highly complex and heterogenic microenvironment, with increasing metabolic status. This environment plays a crucial role in the clinical therapeutic outcome of conventional treatments and innovative antitumor nanomedicines. Scientists have devoted great efforts to conquering the challenges of the tumor microenvironment (TME), in respect of effective drug accumulation and activity at the tumor site. The main focus is to overcome the obstacles of abnormal vasculature, dense stroma, extracellular matrix, hypoxia, and pH gradient acidosis. In this endeavor, nanomedicines that are targeting distinct features of TME have flourished; these aim to increase site specificity and achieve deep tumor penetration. The development of such systems has significantly advanced the application of biomaterials in combinational therapies and in immunotherapies for improved anticancer effectiveness.
  • 287
  • 17 Feb 2024
Topic Review
Heat Shock Proteins-Based Therapies for Cancer
Heat shock proteins (HSPs) are extensively distributed throughout cells. They play a crucial role as molecular chaperones and regulate various cellular processes, such as metabolism, growth, differentiation, cell signaling, and programmed cell death. However, in cancers, HSPs are frequently overexpressed and associated with tumor advancement and metastasis, as well as in acquiring drug resistance against chemotherapeutic agents, leading to poor prognosis. Thus, the expression of HSPs can be modulated to imitate the cellular response against cancer cells by targeting the tumor microenvironment through different mechanisms.
  • 138
  • 17 Feb 2024
Topic Review
Emerging Oral Treatments for Psoriasis
Psoriasis is a chronic inflammatory disease with a worldwide prevalence of 1–3% that can be associated with psoriatic arthritis and other comorbidities and causes a significant burden and impairment of health-related quality of life. Psoriasis is an immune-mediated inflammatory disease (IMID) with a pathogenic admixture of autoinflammatory and autoimmune components and involvement of both innate and adaptive immune systems.
  • 190
  • 17 Feb 2024
Topic Review
NETs Affect the Outcome of Cancer Therapy
Neutrophil extracellular traps (NETs) were originally discovered as a part of the innate immune response of the host to bacteria. They form a web-like structure that can immobilize microorganisms or exhibit direct antimicrobial properties, such as releasing reactive oxygen species (ROS). Resistance to cancer therapy is an important prognostic factor that influences the survival rates of patients. As neutrophil activation and recruitment are present in most solid tumors, it is important to establish if and how the presence of NETs in the tumor microenvironment (TME) might influence the outcome of cancer therapy. In the past, low levels of circulating neutrophils were associated with higher survival rates for patients who underwent different cancer treatments, which was initially considered coincidental.
  • 92
  • 17 Feb 2024
Topic Review
Continuous Interscalene Brachial Plexus Blocks
Brachial plexus blocks at the interscalene level are frequently chosen by physicians and recommended by textbooks for providing regional anesthesia and analgesia to patients scheduled for shoulder surgery. Published data concerning interscalene single-injection or continuous brachial plexus blocks report good analgesic effects. The principle of interscalene catheters is to extend analgesia beyond the duration of the local anesthetic’s effect through continuous infusion, as opposed to a single injection. However, in addition to the recognized beneficial effects of interscalene blocks, whether administered as a single injection or through a catheter, there have been reports of consequences ranging from minor side effects to severe, life-threatening complications. 
  • 122
  • 17 Feb 2024
Topic Review
Therapies for Bone Metastasis in Prostate Cancer
In the absence of early detection and initial treatment, prostate cancer often progresses to an advanced stage, frequently spreading to the bones and significantly impacting patients’ well-being and healthcare resources. Therefore, managing patients with prostate cancer that has spread to the bones often involves using bone-targeted medications like bisphosphonates and denosumab to enhance bone structure and minimize skeletal complications. Additionally, researchers are studying the tumor microenvironment and biomarkers to understand the mechanisms and potential treatment targets for bone metastases in prostate cancer. 
  • 126
  • 17 Feb 2024
Topic Review
Laboratory Tools to Predict CFTR Modulator Effectiveness
The implementation of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator drugs into clinical practice has been attaining remarkable therapeutic outcomes for CF, a life-threatening autosomal recessive genetic disease. However, there is elevated CFTR allelic heterogeneity, and various individuals carrying (ultra)rare CF genotypes remain without any approved modulator therapy. Novel translational model systems based on individuals’ own cells/tissue are now available and can be used to interrogate in vitro CFTR modulator responses and establish correlations of these assessments with clinical features, aiming to provide prediction of therapeutic effectiveness.
  • 151
  • 17 Feb 2024
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