Identification of an IL-22-Dependent Gene Signature as a Pharmacodynamic Biomarker.

Interleukin-22 (IL-22) plays a role in epithelial barrier function and repair, and may provide benefits in conditions like inflammatory bowel disease. However, limited human data are available to assess the clinical effect of IL-22 administration. This study used a human intestinal cell line to identify an IL-22-dependent gene signature that could serve as a pharmacodynamic biomarker for IL-22 therapy.

Efficacy, Safety, and Pharmacodynamic Effects of the Bruton's Tyrosine Kinase Inhibitor Fenebrutinib (GDC-0853) in Systemic Lupus Erythematosus: Results of a Phase II, Randomized, Double-Blind, Placebo-Controlled Trial.

Objective: Fenebrutinib (GDC-0853) is a noncovalent, oral, and highly selective inhibitor of Bruton's tyrosine kinase (BTK). The efficacy, safety, and pharmacodynamics of fenebrutinib in systemic lupus erythematosus (SLE) were assessed in this phase II, multicenter, randomized, placebo-controlled study.

Methods: Patients who had moderately to severely active SLE while receiving background standard therapy were randomized to receive placebo, fenebrutinib 150 mg once daily, or fenebrutinib 200 mg twice daily.

Fenebrutinib versus Placebo or Adalimumab in Rheumatoid Arthritis: A Randomized, Double-Blind, Phase II Trial (ANDES Study).

Objective: To evaluate fenebrutinib, an oral and highly selective non-covalent inhibitor of Bruton's tyrosine kinase (BTK), in patients with active rheumatoid arthritis (RA).

Methods: Patients with RA and inadequate response to methotrexate (cohort 1, n=480) were randomized to fenebrutinib (50 mg once daily, 150 mg once daily, 200 mg twice daily), 40 mg adalimumab every other week, or placebo. Patients with RA and inadequate response to tumor necrosis factor inhibitors (cohort 2, n=98) received fenebrutinib (200 mg twice daily) or placebo.

Family-based prevention programmes for alcohol use in young people.

Background: Alcohol use in young people is a risk factor for a range of short- and long-term harms and is a cause of concern for health services, policy-makers, youth workers, teachers, and parents.

Objectives: To assess the effectiveness of universal, selective, and indicated family-based prevention programmes in preventing alcohol use or problem drinking in school-aged children (up to 18 years of age).Specifically, on these outcomes, the review aimed:• to assess the effectiveness of universal family-based prevention programmes for all children up to 18 years ('universal interventions');• to assess the effectiveness of selective family-based prevention programmes for children up to 18 years at elevated risk of alcohol use or problem drinking ('selective interventions'); and• to assess the effectiveness of indicated family-based prevention programmes for children up to 18 years who are currently consuming alcohol, or who have initiated use or regular use ('indicated interventions').

Nonclinical safety assessment of a human interleukin-22FC IG fusion protein demonstrates in vitro to in vivo and cross-species translatability.

Although Interleukin-22 (IL-22) is produced by various leukocytes, it preferentially targets cells with epithelial origins. IL-22 exerts essential roles in modulating various tissue epithelial functions, such as innate host defense against extracellular pathogens, barrier integrity, regeneration, and wound healing. Therefore, IL-22 is thought to have therapeutic potential in treating diseases associated with infection, tissue injury or chronic tissue damage.

Pre-clinical and translational pharmacology of a human interleukin-22 IgG fusion protein for potential treatment of infectious or inflammatory diseases.

Interleukin (IL)-22 plays protective roles in infections and in inflammatory diseases that have been linked to its meditation of innate immunity via multiple mechanisms. IL-22 binds specifically to its heterodimeric receptor, which is expressed on a variety of epithelial tissues. UTTR1147A is a recombinant fusion protein that links the human cytokine IL-22 with the Fc portion of human immunoglobulin (Ig) G4.

Long-term seizure monitoring using a 256 contact dense array system.

Adapting a 256 contact dense array system to perform multiday long-term EEG and video monitoring requires additional technical attention compared to standard long-term monitoring (LTM). Areas of concern are patient comfort, electrode maintenance, and increased time for record review.

Focus on FOCIS: the continuing diagnostic challenge of autosomal recessive chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a primary immunodeficiency of defective neutrophil oxidative burst activity due to mutations in the genes CYBA, NCF-1, NCF-2, and CYBB, which respectively encode the p22-phox, p47-phox, p67-phox, and gp91-phox subunits. CGD usually presents in early childhood with recurrent or severe infection with catalase-positive bacteria and fungi. We present an unusual case of CGD in which Burkholderia cepacia lymphadenitis developed in a previously healthy 10-year-old girl.

Long polymerase chain reaction-based fluorescence in situ hybridization analysis of female carriers of X-linked chronic granulomatous disease deletions.

Chronic granulomatous disease (CGD) is a rare inherited disorder in which antimicrobial activity of phagocytes is impaired due to the lack of reactive oxygen species, or oxidative burst, produced by NADPH oxidase. The X-linked form of CGD, representing approximately 70% of all cases, is caused by mutations in the cytochrome b beta subunit (CYBB) gene, which maps to chromosome Xp21.1.

Chronic granulomatous disease caused by a deficiency in p47(phox) mimicking Crohn's disease.

We describe 2 cases of autosomal recessive chronic granulomatous disease (CGD) in 2 sisters presenting with a picture consistent with inflammatory bowel disease. The index case is a 10-year-old girl with a history of refractory Crohn's colitis treated with aggressive immunosuppressive therapy whose course subsequently was complicated by central nervous system aspergillosis. Additional evaluation showed a diagnosis of CGD, an underlying immunodeficiency in which phagocytes fail to produce microbicidal reactive oxygen intermediates because of inherited defects in the reduced form of nicotinamide-adenine phosphate dinucleotide (NADPH) oxidase.

Diminished T cell numbers in patients with chronic granulomatous disease.

Chronic granulomatous disease is a neutrophil disorder in which phagocytic cells fail to produce a respiratory burst. Five genetic types of chronic granulomatous disease have been described and in each case the clinical manifestations relate to the inability to effectively kill catalase-positive organisms. It is classically described as a pure disorder of intracellular killing, with preservation of other aspects of phagocytic function such as migration and phagocytosis and normal function of nonmyeloid cells.