Efficacy and safety of an inhaled pan-Janus kinase inhibitor, nezulcitinib, in hospitalised patients with COVID-19: results from a phase 2 clinical trial.

Background: The inhaled lung-selective pan-Janus kinase inhibitor nezulcitinib had favourable safety and potential efficacy signals in part 1 of a phase 2 trial in patients with severe COVID-19, supporting progression to part 2.

Methods: Part 2 was a randomised, double-blind phase 2 study (NCT04402866). Hospitalised patients aged 18-80 years with confirmed symptomatic COVID-19 requiring supplemental oxygen (excluding baseline invasive mechanical ventilation) were randomised 1:1 to nebulised nezulcitinib 3 mg or placebo for up to 7 days with background standard-of-care therapy (including corticosteroids).

A phase 2 multiple ascending dose study of the inhaled pan-JAK inhibitor nezulcitinib (TD-0903) in severe COVID-19.

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Drug-induced skin toxicity: gaps in preclinical testing cascade as opportunities for complex in vitro models and assays.

Skin is the largest organ of the body and serves as the principle barrier to the environment. Composed of multiple cell types arranged in stratified layers with highly specialized appendages, it serves sensory and immune surveillance roles in addition to its primary mechanical function. Several complex in vitro models of skin (i.

Abnormal structure and function of the esophagogastric junction and proximal stomach in gastroesophageal reflux disease.

Objectives: This study applies concurrent magnetic resonance imaging (MRI) and high-resolution manometry (HRM) to test the hypothesis that structural factors involved in reflux protection, in particular, the acute insertion angle of the esophagus into the stomach, are impaired in gastroesophageal reflux disease (GERD) patients.

Methods: A total of 24 healthy volunteers and 24 patients with mild-moderate GERD ingested a test meal. Three-dimensional models of the esophagogastric junction (EGJ) were reconstructed from MRI images.

Toll-like receptor 7 rapidly relaxes human airways.

Rationale: Toll-like receptors (TLRs) 7 and 8 detect respiratory virus single-stranded RNA and trigger an innate immune response. We recently described rapid TLR7-mediated bronchodilation in guinea pigs.

Objectives: To characterize TLR7 expression and TLR7-induced airway relaxation in humans and in eosinophilic airway inflammation in guinea pigs.

The therapeutic potential of Toll-like receptor 7 stimulation in asthma.

Asthma is an inflammatory disorder of the airways frequently characterized by an excessive Th2 adaptive immune response. Activation of Toll-like receptor (TLR)-7, a single-stranded viral RNA receptor that is highly expressed in the airways, triggers a rapid innate immune response and favors a subsequent Th1 response. Because of this role in pulmonary immunoregulation, TLR7 has gained considerable interest as a therapeutic target in asthma.

Toll-like receptor 7 agonists are potent and rapid bronchodilators in guinea pigs.

Background: Respiratory tract viral infections result in asthma exacerbations. Toll-like receptor (TLR) 7 is a receptor for viral single-stranded RNA and is expressed at high levels in the lungs.

Objective: Because TLR7 polymorphisms are associated with asthma, we examined the effects of TLR7 agonists in guinea pig airways.

Gastroesophageal junction: structure and function as assessed by using MR imaging.

Purpose: To develop and validate magnetic resonance (MR) imaging protocols for quantitative assessment of the structural and functional properties of the gastroesophageal junction (GEJ) and to compare MR imaging detection of reflux events against concurrent manometry as a reference method.

Materials And Methods: The local ethics committee approved this study, and written informed consent was obtained. Twelve healthy volunteers were examined.

Effect of meal volume and calorie load on postprandial gastric function and emptying: studies under physiological conditions by combined fiber-optic pressure measurement and MRI.

This study assessed the effects of meal volume (MV) and calorie load (CL) on gastric function. MRI and a minimally invasive fiber-optic recording system (FORS) provided simultaneous measurement of gastric volume and pressure changes during gastric filling and emptying of a liquid nutrient meal in physiological conditions. The gastric response to 12 iso-osmolar MV-CL combinations of a multinutrient drink (MV: 200, 400, 600, 800 ml; CL: 200, 300, 400 kcal) was tested in 16 healthy subjects according to a factorial design.