Topic Review
Cancer-Associated Fibroblast Heterogeneity in Malignancy
Oral squamous cell carcinoma (OSCC) remains an understudied and significant global cancer killer and dismal survival rates have not changed in decades. A better understanding of the molecular basis of OSCC progression and metastasis is needed to develop new approaches for treating this disease. The supportive network surrounding cancer tumor cells known as the tumor microenvironment (TME) has gained increasing interest lately since it performs essential protumorigenic functions. Cancer-associated fibroblasts (CAFs) are one of the main cell types in the TME and are known to play a key role in influencing the biological behavior of tumors.
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  • 22 Mar 2024
Topic Review
PET/MRI for Breast Cancer
The advent of PET/MRI, which combines metabolic PET information with high anatomical detail from MRI, has emerged as a promising tool for breast cancer diagnosis, staging, treatment response assessment, and restaging. Technical advancements including the integration of PET and MRI, considerations in patient preparation, and optimized imaging protocols contribute to the success of dedicated breast and whole-body PET/MRI. 
  • 29
  • 22 Mar 2024
Topic Review
Opioid-Induced Constipation in Cancer Patients
Opioid-induced constipation (OIC) is a disabling symptom which 60–90 percent of cancer patients with chronic opioid use experience. Peripherally acting μ-opioid receptor antagonists (PAMORAs) are a class of medications aiming to reverse opioids’ adverse effects on the gut by interacting with opioid receptors in the gastrointestinal tract without significantly crossing the blood–brain barrier, and therefore they are not affecting the analgesic opioid effects in the central nervous system.
  • 30
  • 22 Mar 2024
Topic Review
Flavonoids as CYP3A4 Inhibitors In Vitro
CYP enzymes are a group of heme-containing enzymes that play important roles in the metabolism of many drugs and other xenobiotics. They are located in the endoplasmic reticulum of cells throughout the body, but they are most abundant in the liver.
  • 26
  • 22 Mar 2024
Topic Review
Treatment of Cisplatin/Platinum-Ineligible Metastatic Urothelial Carcinoma
Metastatic urothelial cancer (mUC) is an aggressive malignancy with limited treatment options. Cisplatin-based chemotherapy has been the standard of care in metastatic urothelial cancer (mUC). However, many patients with comorbidities cannot receive cisplatin or its alternative, carboplatin. ‘Cisplatin-ineligible’ and ‘platinum-ineligible’ patients lacked effective therapy options. However, the combination of enfortumab vedotin (EV), an antibody–drug conjugate targeting Nectin-4, with pembrolizumab (P), an antibody targeting the programmed death-1 (PD-1) immune checkpoint, is changing the status quo of frontline mUC treatment, with potential synergy seen in the EV-103 and EV-302 clinical trials.
  • 44
  • 22 Mar 2024
Topic Review
Infections in Disorders of Immune Regulation
Primary immune regulatory disorders (PIRDs) constitute a spectrum of inborn errors of immunity (IEIs) that are primarily characterized by autoimmunity, lymphoproliferation, atopy, and malignancy. In PIRDs, infections are infrequent compared to other IEIs. While susceptibility to infection primarily stems from antibody deficiency, it is sometimes associated with additional innate immune and T or NK cell defects. The use of immunotherapy and chemotherapy further complicates the immune landscape, increasing the risk of diverse infections. Recurrent sinopulmonary infections, particularly bacterial infections such as those associated with staphylococcal and streptococcal organisms, are the most reported infectious manifestations. Predisposition to viral infections, especially Epstein–Barr virus (EBV)-inducing lymphoproliferation and malignancy, is also seen. Notably, mycobacterial and invasive fungal infections are rarely documented in these disorders. Knowledge about the spectrum of infections in these disorders would prevent diagnostic delays and prevent organ damage. 
  • 50
  • 22 Mar 2024
Topic Review
Classification and Hemodynamic Definitions of Pulmonary Hypertension
Pulmonary hypertension (PH) refers to a pathologic elevation of the mean pulmonary artery pressure (mPAP) and is associated with increased morbidity and mortality in a wide range of medical conditions. These conditions are classified according to similarities in pathophysiology and management in addition to their invasive hemodynamic profiles. The 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension present the newest clinical classification system and includes significant updates to the hemodynamic definitions. Pulmonary hypertension is now hemodynamically defined as an mPAP > 20 mmHg, reduced from the previous threshold of ≥25 mmHg, due to important insights from both normative and prognostic data. Pulmonary vascular resistance has been extended into the definition of pre-capillary pulmonary hypertension, with an updated threshold of >2 Wood Units (WU), to help differentiate pulmonary vascular disease from other causes of increased mPAP. Exercise pulmonary hypertension has been reintroduced into the hemodynamic definitions and is defined by an mPAP/cardiac output slope of >3 mmHg/L/min between rest and exercise. While these new hemodynamic thresholds will have a significant impact on the diagnosis of pulmonary hypertension, no evidence-based treatments are available for patients with mPAP between 21–24 mmHg and/or PVR between 2–3 WU or with exercise PH. 
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  • 21 Mar 2024
Topic Review Peer Reviewed
The Effects of SARS-CoV-2 on the Angiopoietin/Tie Axis and the Vascular Endothelium
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause potentially life-threatening coronavirus disease (COVID-19). COVID-19 is a multisystem disease and is associated with significant respiratory distress, systemic hyperinflammation, vasculitis, and multi-organ failure. SARS-CoV-2 causes the deterioration of numerous systems, with increasing evidence implying that COVID-19 affects the endothelium and vascular function. The endothelium is important for preserving vascular tone and homeostasis. The overactivation and dysfunction of endothelial cells are significant outcomes of severity in patients with COVID-19. The Angiopoietin 1/Tie 2 pathway plays an important role in endothelium quiescence and vessel stability. The disruption of Angiopoietin/Tie balance affects the vessel contact barrier and leads to vessel leakage, and this in turn causes endothelial dysfunction. Although vascular instability through SARS-CoV-2 is associated with endothelial dysfunction, it is still not understood if the virus affects the Angiopoietin/Tie axis directly or via other mechanisms such as cytokine storm and/or immune response associated with the infection. This review provides an overview of the impact SARS-CoV-2 has on endothelial function and more specifically on the Angiopoietin/Tie pathway.
  • 245
  • 21 Mar 2024
Topic Review
The Single Toxin Origin of Alzheimer’s Disease
New data suggest that the aggregation of misfolded native proteins initiates and drives the pathogenic cascade that leads to Alzheimer’s disease (AD) and other age-related neurodegenerative disorders. Researchers propose a unifying single toxin theory of brain neurodegeneration that identifies new targets and approaches to the development of disease-modifying treatments. An extensive body of genetic evidence suggests soluble aggregates of beta-amyloid (Aβ) as the primary neurotoxin in the pathogenesis of AD. New insights from fluid biomarkers, imaging, and clinical studies provide further evidence for the decisive impact of toxic Aβ species in the initiation and progression of AD.
  • 27
  • 21 Mar 2024
Topic Review
Development of Pre-Eclampsia
Pre-eclampsia is a serious complication of pregnancy characterized by a state of multiorgan hypertensive disorders, with or without proteinuria and possible multiorgan dysfunction.
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  • 21 Mar 2024
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