Inhibition of Receptor-Interacting Protein Kinase 1 in Chronic Plaque Psoriasis: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study.

Introduction: Receptor-interacting protein kinase 1 (RIPK1), a key mediator of inflammation through necroptosis and proinflammatory cytokine production, may play a role in the pathogenesis of immune-mediated inflammatory diseases such as chronic plaque psoriasis. An experimental medicine study of RIPK1 inhibition with GSK2982772 immediate-release formulation at doses up to 60 mg three times daily in mild to moderate plaque psoriasis indicated that efficacy may be improved with higher trough concentrations of GSK2982772.

Methods: This multicenter, randomized, double-blind, placebo-controlled, repeat-dose study (NCT04316585) assessed the efficacy, safety, pharmacokinetics, and pharmacodynamics of 960 mg GSK2982772 (once-daily modified-release formulation) in patients with moderate to severe plaque psoriasis.

Study to Explore the Association of the Renin-Angiotensin System and Right Ventricular Function in Mechanically Ventilated Patients.

Background: Right ventricular () dysfunction is associated with pulmonary vasoconstriction in mechanically ventilated patients. Enhancing the activity of angiotensin-converting enzyme 2 (2), a key enzyme of the renin-angiotensin system (), using recombinant human 2 (2) could alleviate -mediated vasoconstriction and vascular remodeling.

Methods: This prospective observational study investigated the association between concentrations of peptides (Ang II or Ang(1-7)) and markers of function, as assessed by echocardiography (ratio of to left ventricular end-diastolic area, interventricular septal motion, and pulmonary arterial systolic pressure ()).

An open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of GSK2586881 in participants with pulmonary arterial hypertension.

Preclinical and early clinical studies suggest that angiotensin-converting enzyme type 2 activity may be impaired in patients with pulmonary arterial hypertension (PAH); therefore, administration of exogenous angiotensin-converting enzyme type 2 (ACE2) may be beneficial. This Phase IIa, multi-center, open-label, exploratory, single-dose, dose-escalation study (NCT03177603) assessed the potential vasodilatory effects of single doses of GSK2586881 (a recombinant human ACE2) on acute cardiopulmonary hemodynamics in hemodynamically stable adults with documented PAH who were receiving background PAH therapy. Successive cohorts of participants were administered a single intravenous dose of GSK2586881 of 0.

Pruritus in the Pediatric Burn Population.

Postburn pruritus is a significant issue that can have a devastating impact on patient quality of life. Despite its known negative impact, few studies have focused on the pediatric population. Thus, the aim of this study was to determine the incidence of pruritus among pediatric burn patients as well as identify its predictive factors and commonly used treatments, including the novel use of laser therapy.

Effects of Recombinant Human Angiotensin-Converting Enzyme 2 on Response to Acute Hypoxia and Exercise: A Randomised, Placebo-Controlled Study.

Introduction: Angiotensin-converting enzyme 2 (ACE2) is a key enzyme of the renin-angiotensin system (RAS) that has been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS). Enhancing ACE2 activity using GSK2586881, a recombinant form of human ACE2, could be beneficial in diseases such as ARDS but may blunt the hypoxic pulmonary vasoconstriction (HPV) response and potentially impact systemic and tissue oxygenation. This study aimed to evaluate the effect of GSK2586881 0.