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Topic Review
Biologic Therapy for Inflammatory Bowel Disease Patients
Many patients with inflammatory bowel disease (IBD) experience a loss of effectiveness to biologic therapy (i.e., anti-TNF therapy, etc.). Therefore, in addition to the adverse effects of the treatment, these patients also face failure to achieve and maintain remission. Immunogenicity, the process of production of antibodies to biological agents, is fundamental to the evolution of loss of response to treatment in IBD patients.
  • 88
  • 07 Mar 2024
Topic Review
Human Cytomegalovirus (HCMV) Genetic Diversity and Drug Resistance
Human cytomegalovirus (HCMV) is a pathogen with high prevalence in the general population that is responsible for high morbidity and mortality in immunocompromised individuals and newborns, while remaining mainly asymptomatic in healthy individuals. The HCMV genome is 236,000 nucleotides long and encodes approximately 200 genes in more than 170 open reading frames, with the highest rate of genetic polymorphisms occurring in the envelope glycoproteins. HCMV infection is treated with antiviral drugs such as ganciclovir, valganciclovir, cidofovir, foscarnet, letermovir and maribavir targeting viral enzymes, DNA polymerase, kinase and the terminase complex. One of the obstacles to successful therapy is the emergence of drug resistance, which can be tested phenotypically or by genotyping using Sanger sequencing, which is a widely available but less sensitive method, or next-generation sequencing performed in samples with a lower viral load to detect minority variants, those representing approximately 1% of the population. The prevalence of drug resistance depends on the population tested, as well as the drug, and ranges from no mutations detected to up to almost 50%. A high prevalence of resistance emphasizes the importance of testing the patient whenever resistance is suspected, which requires the development of more sensitive and rapid tests while also highlighting the need for alternative therapeutic targets, strategies and the development of an effective vaccine.
  • 90
  • 07 Mar 2024
Topic Review
Long-Term Mechanical Circulatory Support Devices
Cardiovascular disease (CVD) includes a range of disorders that affect the myocardium and/or the vascular system. It stands as the number one cause of death worldwide, accounting for one-third of all deaths. The prevalence of CVD contributes to the rise in healthcare costs, which is attributed to increased rates of hospitalisation, primary care usage and prescription medication. Heart failure (HF) is a common clinical syndrome caused by functional and structural abnormalities of the heart, imposing a burden of disability, reduced quality of life and increased mortality rate. Durable mechanical circulatory support (MCS) devices have become progressively more common as a long-term therapeutic option. Many patients are initially deemed eligible for MCS device implantation as a bridge to transplant but face the harsh reality of limited organ availability. 
  • 157
  • 07 Mar 2024
Topic Review
Endothelial Senescence
Endothelial cells line at the most inner layer of blood vessels. They act to control hemostasis, arterial tone/reactivity, wound healing, tissue oxygen, and nutrient supply. With age, endothelial cells become senescent, characterized by reduced regeneration capacity, inflammation, and abnormal secretory profile. Endothelial senescence represents one of the earliest features of arterial ageing and contributes to many age-related diseases. Compared to those in arteries and veins, endothelial cells of the microcirculation exhibit a greater extent of heterogeneity. Microcirculatory endothelial senescence leads to a declined capillary density, reduced angiogenic potentials, decreased blood flow, impaired barrier properties, and hypoperfusion in a tissue or organ-dependent manner. The heterogeneous phenotypes of microvascular endothelial cells in a particular vascular bed and across different tissues remain largely unknown. Accordingly, the mechanisms underlying macro- and micro-vascular endothelial senescence vary in different pathophysiological conditions, thus offering specific target(s) for therapeutic development of senolytic drugs.
  • 135
  • 07 Mar 2024
Topic Review
Mycobacterium avium ssp. paratuberculosis and Crohn’s Disease
Mycobacterium avium ssp. paratuberculosis (MAP) is the cause of Johne’s disease (JD), which is a chronic infectious gastrointestinal disease of ruminants and is often fatal. In humans, MAP has been associated with Crohn’s disease (CD) for over a century, without conclusive evidence of pathogenicity. Numerous researchers have contributed to the subject, but there is still a need for evidence of the causation of CD by MAP.
  • 162
  • 07 Mar 2024
Topic Review
Pathophysiology-Based Traumatic Brain Injury
Traumatic brain injury (TBI) is a leading cause of disability and death among children and young adults, with an incidence of approximately 1.7 million per year in the USA, resulting in 52,000 deaths. Survivors of the initial impact must still contend with the consequences of trauma, as not all injury occurs at the time of impact. The primary injury results from forces applied to the head and involve direct structural damage to the brain. This triggers a cascade of events leading to neurological damage that evolves secondary injury. Several external brain insults, both intracranial and systemic, may complicate and worsen the secondary injury.
  • 505
  • 07 Mar 2024
Topic Review
Pigmented Purpuric Dermatoses
Pigmented purpuric dermatoses (PPD) encompass a group of chronic skin conditions characterized by the presence of petechiae, purpura, and pigmentation changes.
  • 209
  • 07 Mar 2024
Topic Review
Tau Pathology in Alzheimer’s Disease and Down Syndrome
Individuals with Down syndrome (DS) exhibit an almost complete penetrance of Alzheimer’s disease (AD) pathology but are underrepresented in clinical trials for AD. The Tau protein is associated with microtubule function in the neuron and is crucial for normal axonal transport. In several different neurodegenerative disorders, Tau misfolding leads to hyper-phosphorylation of Tau (p-Tau), which may seed pathology to bystander cells and spread.
  • 175
  • 07 Mar 2024
Topic Review
Gastroesophageal Reflux Disease following Sleeve Gastrectomy
Obesity is associated with serious comorbidities and economic implications. Bariatric surgery, most commonly Roux-en-Y gastric bypass and sleeve gastrectomy, are effective options for weight loss and the improvement of obesity-related comorbidities. With the growing obesity epidemic, there has been a concomitant rise in bariatric surgeries, particularly in sleeve gastrectomy. Gastroesophageal reflux disease (GERD) is highly prevalent in obese individuals, can significantly impact quality of life and may lead to serious complications. Obesity and GERD both improve with weight loss.
  • 93
  • 07 Mar 2024
Topic Review
Structural and Functional Arterial Properties
Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with adverse cardiovascular (CV) outcomes. Vascular aging (VA), which is defined as the progressive deterioration of arterial function and structure over a lifetime, is an independent predictor of both AF development and CV events. A timing identification and treatment of early VA has therefore the potential to reduce the risk of AF incidence and related CV events. 
  • 100
  • 07 Mar 2024
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