Development of a novel air-liquid interface airway tissue equivalent model for in vitro respiratory modeling studies.

The human airways are complex structures with important interactions between cells, extracellular matrix (ECM) proteins and the biomechanical microenvironment. A robust, well-differentiated in vitro culture system that accurately models these interactions would provide a useful tool for studying normal and pathological airway biology. Here, we report the development and characterization of a physiologically relevant air-liquid interface (ALI) 3D airway 'organ tissue equivalent' (OTE) model with three novel features: native pulmonary fibroblasts, solubilized lung ECM, and hydrogel substrate with tunable stiffness and porosity.

Organoid Technologies for SARS-CoV-2 Research.

Purpose Of Review: Organoids are an emerging technology utilizing three-dimensional (3D), multi-cellular in vitro models to represent the function and physiological responses of tissues and organs. By using physiologically relevant models, more accurate tissue responses to viral infection can be observed, and effective treatments and preventive strategies can be identified. Animals and two-dimensional (2D) cell culture models occasionally result in inaccurate disease modeling outcomes.

Long- and short-term outcomes in renal allografts with deceased donors: A large recipient and donor genome-wide association study.

Improvements in immunosuppression have modified short-term survival of deceased-donor allografts, but not their rate of long-term failure. Mismatches between donor and recipient HLA play an important role in the acute and chronic allogeneic immune response against the graft. Perfect matching at clinically relevant HLA loci does not obviate the need for immunosuppression, suggesting that additional genetic variation plays a critical role in both short- and long-term graft outcomes.

Safety, Pharmacokinetics, and Immunogenicity of Obiltoxaximab After Intramuscular Administration to Healthy Humans.

Inhalational anthrax is a highly lethal infection caused by Bacillus anthracis and a serious bioterrorism threat. Protective antigen (PA) is a critical component required for the virulence of Bacillus anthracis. Obiltoxaximab, a high-affinity monoclonal antibody that neutralizes PA, is approved in the United States for intravenous use for the treatment of inhalational anthrax in combination with appropriate antibacterial drugs and for prophylaxis of inhalational anthrax when alternative therapies are not available or appropriate.

3D printed mitral valve models: affordable simulation for robotic mitral valve repair.

Objectives: 3D printed mitral valve (MV) models that capture the suture response of real tissue may be utilized as surgical training tools. Leveraging clinical imaging modalities, 3D computerized modelling and 3D printing technology to produce affordable models complements currently available virtual simulators and paves the way for patient- and pathology-specific preoperative rehearsal.

Methods: We used polyvinyl alcohol, a dissolvable thermoplastic, to 3D print moulds that were casted with liquid platinum-cure silicone yielding flexible, low-cost MV models capable of simulating valvular tissue.

Vedolizumab Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability Following Administration of a Single, Ascending, Intravenous Dose to Healthy Volunteers.

Background And Objectives: Vedolizumab, a humanized monoclonal antibody against the αβ integrin, is indicated for treatment of moderately to severely active ulcerative colitis or Crohn's disease. In this placebo-controlled, double-blind, randomized, single ascending-dose study, the pharmacokinetics, pharmacodynamics, safety, and tolerability of vedolizumab were evaluated in healthy volunteers.

Methods: Forty-nine participants (in five cohorts) were randomly assigned in a 4:1 ratio to receive a single intravenous infusion of either vedolizumab (0.

Pharmacokinetics and Tolerability of Obiltoxaximab: A Report of 5 Healthy Volunteer Studies.

Purpose: This report describes the safety, immunogenicity, and pharmacokinetic results of obiltoxaximab treatment in healthy subjects from 5 clinical trials.

Methods: Healthy men and women were enrolled in randomized, double-blind studies of obiltoxaximab versus placebo (studies 1-3), an open-label, parallel-group study of obiltoxaximab alone versus obiltoxaximab and ciprofloxacin (study 4), or a randomized, double-blind, placebo-controlled study involving administration of a second dose of obiltoxaximab 13 or 119 days after an initial dose (study 5). Obiltoxaximab was administered intravenously in all studies.

Occurrence of adverse events among patients with inflammatory bowel disease in the HealthCore Integrated Research Database.

Objectives: Inflammatory bowel disease (IBD) is a chronic condition commonly requiring lifelong care. Both IBD and IBD-related treatments can cause significant morbidity, and it is often difficult to differentiate their relative etiologic contribution to adverse events (AEs). The objectives of this study were to assess the rates of select AEs among patients with IBD as a function of disease severity and of the use of anti-tumor necrosis factor alpha (anti-TNFα) medications.

Long-term clinical experience with vedolizumab in patients with inflammatory bowel disease.

Background: Vedolizumab, a gut-selective, anti-inflammatory monoclonal antibody, has shown preliminary efficacy in ulcerative colitis (UC) and Crohn's disease (CD). We report long-term experience with vedolizumab for active UC and CD.

Methods: After a placebo-controlled study, 38 patients with UC were randomized to a loading regimen of vedolizumab 2, 6, or 10 mg/kg on days 1, 15, and 43, followed by maintenance dosing every 8 weeks.

Vedolizumab for the treatment of active ulcerative colitis: a randomized controlled phase 2 dose-ranging study.

Background: Vedolizumab is a gut-selective biologic that has shown efficacy in ulcerative colitis (UC) and Crohn's disease (CD). We studied the pharmacokinetics, pharmacodynamics, safety, tolerability, and efficacy of a new formulation of vedolizumab produced by an improved manufacturing process.

Methods: UC patients were randomized to receive vedolizumab (2, 6, or 10 mg/kg) or placebo on days 1, 15, 29, and 85.

MLN3897 plus methotrexate in patients with rheumatoid arthritis: safety, efficacy, pharmacokinetics, and pharmacodynamics of an oral CCR1 antagonist in a phase IIa, double-blind, placebo-controlled, randomized, proof-of-concept study.

Objective: To assess the efficacy, safety, pharmacokinetics, and pharmacodynamics of the CC chemokine receptor CCR1 antagonist MLN3897 in patients with rheumatoid arthritis (RA) receiving methotrexate (MTX).

Methods: In this phase IIa, proof-of-concept study, patients meeting the American College of Rheumatology (ACR) criteria for RA who had been taking MTX for >or=6 months with evidence of active disease were randomly assigned to receive either 10 mg oral MLN3897 or matching placebo once daily for 12 weeks (days 1-83) while continuing to receive MTX once a week. Clinical assessments, safety monitoring, and sampling for pharmacokinetic and pharmacodynamic analyses were performed throughout the study.