Treatment modalities for infantile spasms: current considerations and evolving strategies in clinical practice.

Infantile spasms, newly classified as infantile epileptic spasm syndrome (IESS), occur in children under 2 years of age and present as an occur as brief, symmetrical, contractions of the musculature of the neck, trunk, and extremities. When infantile spasms occur with a concomitant hypsarrhythmia on electroencephalogram (EEG) and developmental regression, it is known as West Syndrome. There is no universally accepted mainstay of treatment for this condition, but some options include synthetic adrenocorticotropic hormone (ACTH), repository corticotropin injection (RCI/Acthar Gel), corticosteroids, valproic acid, vigabatrin, and surgery. Without effective treatment, infantile spasms can cause an impairment of psychomotor development and/or cognitive and behavioral functions. The first-line treatment in the USA is ACTH related to high efficacy for cessation of infantile spasms long-term and low-cost profile. Acthar Gel is a repository corticotropin intramuscular injection that became FDA-approved for the treatment of IESS in 2010. Though it is believed that ACTH, Acthar Gel, and corticosteroids all work via a negative feedback pathway to decrease corticotropin-releasing hormone (CRH) release, their safety and efficacy profiles all vary. Vigabatrin and valproic acid are both anti-seizure medications that work by increasing GABA concentrations in the CNS and decreasing excitatory activity. Acthar Gel has been shown to have superior efficacy and a diminished side effect profile when compared with other treatment modalities.

The Evolving Role of Vericiguat in Patients With Chronic Heart Failure.

Heart failure (HF) is a chronic and progressive clinical disorder characterized by an inability to pump sufficient blood to meet metabolic demands. It poses a substantial global healthcare burden, leading to high morbidity, mortality, and economic impact. Current treatments for HF include lifestyle modifications, guideline-directed medical therapies (GDMT), and device interventions, but the need for novel therapeutic approaches remains significant. The introduction of vericiguat, a soluble guanylate cyclase stimulator, has shown promise in improving outcomes for heart failure patients. Vericiguat addresses the underlying pathophysiological mechanisms of heart failure by augmenting the cyclic guanosine monophosphate (cGMP) pathway, leading to enhanced cardiac contractility and vasodilation. Clinical trials evaluating the efficacy and safety of vericiguat, such as the Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA) trial, have demonstrated promising results. It has been shown that vericiguat, when added to standard therapy, reduces the risk of HF hospitalization and cardiovascular death in patients with symptomatic chronic HF with reduced ejection fraction (HFrEF). The addition of vericiguat to the current armamentarium of HF treatments provides clinicians with a novel therapeutic option to further optimize patient outcomes. Its potential benefits extend beyond symptom management, aiming to reduce hospitalizations and mortality rates associated with HF. As with any new treatment, the appropriate patient selection, monitoring, and management of potential adverse effects are essential. Further research is warranted to determine the long-term benefits, optimal dosing strategies, and potential combination therapies involving vericiguat. Its ability to target the cGMP pathway provides a unique mechanism of action, offering potential benefits in improving clinical outcomes for HF patients. Continued investigation and clinical experience will further elucidate the role of vericiguat in the management of HF and its overall impact on reducing the healthcare burden associated with this debilitating condition.

Angiotensin-Converting Enzyme Inhibitors and Other Medications Associated With Angioedema.

Angioedema is a localized swelling of the dermis, subcutaneous tissues, and/or submucosal tissues caused by fluid extravasation into these tissues. Angioedema is associated with certain vasoactive molecules and is typically mediated by histamine or bradykinin. It manifests clinically as facial edema, swelling of the extremities and urogenital area, and potential involvement of the larynx, leading to dyspnea and inspiratory stridor, which can become life-threatening. Histamine-mediated angioedema is associated with urticaria and pruritus and will show classic signs of allergic (type 1 hypersensitivity) reactions. Bradykinin-mediated angioedema is often familial (hereditary angioedema) and is more often associated with gastrointestinal symptoms (abdominal pain, nausea, vomiting, diarrhea), edema of the extremities and trunk, and a lack of urticaria and pruritus. Angiotensin-converting enzyme inhibitors (ACEIs) are a class of medications commonly prescribed for hypertension, heart failure, and diabetic nephropathy. ACEIs are associated with an increased risk of angioedema, which can range from a mild reaction to severe and life-threatening. ACEI-induced angioedema is a bradykinin-mediated reaction that can occur in individuals with a genetic predisposition. Other medications, such as angiotensin receptor blockers, nonsteroidal anti-inflammatory drugs, and certain antibiotics, most notably those in the beta-lactam class, can also cause drug-induced angioedema. The present investigation describes current knowledge of the pathophysiology, epidemiology, clinical manifestations, predisposing factors, and management of drug-induced angioedema.