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Topic Review
From CGRP to PACAP: Novel Antimigraine Drug Targets
Migraine is a neurovascular disorder that can be debilitating for individuals and society. Current research focuses on finding effective analgesics and management strategies for migraines by targeting specific receptors and neuropeptides. Nonetheless, newly approved calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) have a 50% responder rate ranging from 27 to 71.0%, whereas CGRP receptor inhibitors have a 50% responder rate ranging from 56 to 71%. To address the need for novel therapeutic targets, researchers are exploring the potential of another secretin family peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), as a ground-breaking treatment avenue for migraine. Preclinical models have revealed how PACAP affects the trigeminal system, which is implicated in headache disorders. Clinical studies have demonstrated the significance of PACAP in migraine pathophysiology; however, a few clinical trials remain inconclusive: the pituitary adenylate cyclase-activating peptide 1 receptor mAb, AMG 301 showed no benefit for migraine prevention, while the PACAP ligand mAb, Lu AG09222 significantly reduced the number of monthly migraine days over placebo in a phase 2 clinical trial. Meanwhile, another secretin family peptide vasoactive intestinal peptide (VIP) is gaining interest as a potential new target.
  • 328
  • 21 Nov 2023
Topic Review
Multiparametric Magnetic Resonance Imaging of Penile Cancer
Primary penile cancer is an uncommon malignancy with an incidence ranging from up to 6.8 per 100,000 in Africa, Asia, and South America to less than 1 per 100,000 in North America and Europe. Accurate preoperative staging and precise outlining of a tumor’s extent are crucial for selecting the most suitable treatment approach and improving outcomes. The current clinical staging of penile cancer is still largely based on physical examination. Multiparametric magnetic resonance imaging (mpMRI) is an important imaging modality that complements physical examination and reduces uncertainties that can easily arise during this examination.
  • 411
  • 21 Nov 2023
Topic Review
Janus-Faced Role of Autophagy in Hepatocellular Carcinoma
Autophagy is a multi-step catabolic process that occurs in cells at a basal level and is triggered by various stressors that disrupt cellular homeostasis. These stressors can include low levels of cellular ATP, nutrient and growth factor deficiencies, hypoxia, endoplasmic reticulum (ER) stress, pathogen entry, or exposure to anticancer drugs. 
  • 350
  • 21 Nov 2023
Topic Review
New-Onset Atrial Fibrillation in Severe COVID-19 Patients
New-onset atrial fibrillation (NOAF) is the most frequently encountered cardiac arrhythmia observed in patients with COVID-19 infection, particularly in Intensive Care Unit (ICU) patients. The proposed mechanisms that could contribute to the development of Atrial fibrillation (AF) in these patients include myocardial damage resulting from direct virus-induced cardiac injury, potentially leading to perimyocarditis; a cytokine crisis and heightened inflammatory response; hypoxemia due to acute respiratory distress; disturbances in acid-base and electrolyte levels; as well as the frequent use of adrenergic drugs in critically ill patients.
  • 116
  • 21 Nov 2023
Topic Review
Soluble ST2 Biology
ST2 is a member of the interleukin (IL)-1 receptor family, whose gene is located on human chromosome 2q12. Alternative promoter splicing and 3′ processing of the mRNA are responsible for the production of two different forms: a soluble receptor, named sST2; or a transmembrane receptor, named ST2L. ST2 was first described in 1989.
  • 281
  • 21 Nov 2023
Topic Review
COVID-19 and Kidney Disease
Chronic kidney disease (CKD) is the most common risk factor for severe COVID-19 and one that most increases the risk of COVID-19-related death. Moreover, CKD increases the risk of acute kidney injury (AKI), and COVID-19 patients with AKI are at an increased risk of death.
  • 147
  • 21 Nov 2023
Topic Review
Liquid Biopsies for Monitoring in Metastatic Breast Cancer
In breast cancer patients, a blood sample contains components from tumor origin as well as those influenced by the tumor disease. Analyzing blood as a so-called liquid biopsy in breast cancer (BC) patients has the potential to adapt therapy management. Circulating tumor cells (CTCs), extracellular vesicles (EVs), cell-free DNA (cfDNA) and other blood components mirror the tumoral heterogeneity and could support a range of clinical decisions. In a subgroup of breast cancer patients, the detection of mutations in a specific gene using cell-free DNA from blood might be suitable for therapy monitoring. An interventional trial confirmed a significant outcome benefit when therapy was changed in case of newly emerging cfDNA mutations under treatment and thus showed the clinical utility of cfDNA analysis for therapy monitoring. Monitoring value is defined as (1) the association of a laboratory result from a blood sample drawn under therapy with the clinically and/or radiographically proven therapy response or (2) the association of a laboratory result from a blood sample drawn under therapy with the prognosis of the disease/therapy in the course of time.
  • 129
  • 21 Nov 2023
Topic Review
Vortioxetine´s Effects on Sleep of Adolescent Major Depression
The relationship between depression and insomnia is bidirectional and both conditions need to be treated adequately, especially in a vulnerable neurodevelopmental stage of adolescence. Sleep disturbances in adolescents have been associated with a more severe clinical course of depression (i.e., suicidal behavior, worse psychosocial functioning, and risk of recurrence). Due to the rising incidence of both disorders, it is crucial to understand the underlying pathophysiology (e.g., disrupted neuroplasticity and neurotransmitter dysbalance), especially in the vulnerable adolescent age period characterized by developmental changes and sensitivity to endogenous and exogenous factors.
  • 164
  • 20 Nov 2023
Topic Review
Consequence of Alveolar Hyperoxia and Systemic Hyperoxaemia
Acute hypoxic respiratory failure (AHRF) is a prominent feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) critical illness. The need for a high FiO2 to normalise arterial hypoxemia and tissue hypoxia can result in alveolar hyperoxia. This in turn can lead to local alveolar oxidative stress with associated inflammation, alveolar epithelial cell apoptosis, surfactant dysfunction, pulmonary vascular abnormalities, resorption atelectasis, and impairment of innate immunity predisposing to secondary bacterial infections. While oxygen is a life-saving treatment, alveolar hyperoxia may exacerbate pre-existing lung injury.
  • 434
  • 20 Nov 2023
Topic Review
Second Tumors in Retinoblastoma Survivors after Ionizing Radiation
Retinoblastoma (RB) is the most common ocular neoplasm in children, whose development depends on two mutational events that occur in both alleles of the retinoblastoma susceptibility gene (RB1). Regarding the nature of these mutational events, RB can be classified as hereditary if the first event is a germline mutation and the second one is a somatic mutation in retina cells or nonhereditary if both mutational events occur in somatic cells. Although the rate of survival of RB is significantly elevated, the incidence of second malignant neoplasms (SMNs) is a concern, since SMNs are the main cause of death in these patients. Furthermore, evidence confirms that hereditary RB survivors are at a higher risk for SMNs than nonhereditary RB survivors. This risk seems to increase with the use of ionizing radiation in some therapeutic approaches commonly used in the treatment of RB.
  • 147
  • 20 Nov 2023
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