Pharmacodynamic Exposure-Response Analysis of Fracture Count Data Following Treatment with Burosumab in Patients with XLH.

X-linked hypophosphatemia (XLH) is a rare genetic disorder caused by excessive fibroblast growth factor 23 (FGF23), leading to low serum phosphate levels resulting in increased risk of fractures and pseudofractures. Burosumab is indicated for the treatment of XLH. In this work, we aimed to understand the quantitative relationship between burosumab-treatment-induced improvements in serum phosphate and reduction in fracture and pseudofracture counts in adults with XLH.

Item Response Theory Quantifies the Relationship Between Improvements in Serum Phosphate and Patient-Reported Outcomes in Adults With X-Linked Hypophosphatemia.

Burosumab is indicated for treatment of a rare bone disease, X-linked hypophosphatemia (XLH). The aim of this analysis was to evaluate the relationship between a treatment response biomarker and patient-reported outcomes (PROs). Longitudinal data for PROs were obtained from adults with XLH from a phase III study.

Developing Smartphone-Based Objective Assessments of Physical Function in Rheumatoid Arthritis Patients: The PARADE Study.

Background: Digital biomarkers that measure physical activity and mobility are of great interest in the assessment of chronic diseases such as rheumatoid arthritis, as it provides insights on patients' quality of life that can be reliably compared across a whole population.

Objective: To investigate the feasibility of analyzing iPhone sensor data collected remotely by means of a mobile software application in order to derive meaningful information on functional ability in rheumatoid arthritis patients.

Methods: Two objective, active tasks were made available to the study participants: a wrist joint motion test and a walk test, both performed remotely and without any medical supervision.

Using a ResearchKit Smartphone App to Collect Rheumatoid Arthritis Symptoms From Real-World Participants: Feasibility Study.

Background: Using smartphones to enroll, obtain consent, and gather self-reported data from patients has the potential to enhance our understanding of disease burden and quantify physiological impact in the real world. It may also be possible to harness integral smartphone sensors to facilitate remote collection of clinically relevant data.

Objective: We conducted the Patient Rheumatoid Arthritis Data From the Real World (PARADE) observational study using a customized ResearchKit app with a bring-your-own-device approach.

Safety of Repeated Open-Label Treatment Courses of Intravenous Ofatumumab, a Human Anti-CD20 Monoclonal Antibody, in Rheumatoid Arthritis: Results from Three Clinical Trials.

Objectives: To investigate the safety of ofatumumab retreatment in rheumatoid arthritis.

Methods: Patients with active rheumatoid arthritis participating in two phase III trials (OFA110635 and OFA110634) and a phase II extension trial (OFA111752) received individualised open-label ofatumumab retreatment (700 mg X 2 intravenous infusions two weeks apart) ≥24 weeks following the first course and ≥16 weeks following further courses. Retreatment required evidence of clinical response followed by disease relapse.

Epidemiology and Treatment of New-Onset and Established Rheumatoid Arthritis in an Insured US Population.

Objective: To investigate the epidemiology and treatment of rheumatoid arthritis (RA) in a population broadly representative of employed adults in the US, using a retrospective cohort design.

Methods: Incident and prevalent RA cohorts were defined from a sample of 4.66 million adults with complete followup data from the period of January 2005 through September 2008 in the Pharmetrics medical claims database.

Apoptotic-like tumor cells and apoptotic neutrophils in mitochondrion-rich gastric adenocarcinomas: a comparative study with light and electron microscopy between these two forms of cell death.

Mitochondrion-rich adenocarcinomas represent a rare variant of gastric adenocarcinomas composed predominantly of columnar adenocarcinoma cells with eosinophilic cytoplasm, a strong supranuclear immunoreactivity for antimitochondrial antibody, and a marked neutrophil infiltration associated to tumor cell death. The purpose of this work is to investigate, using correlated light and electron microscopy, mitochondrion-rich gastric adenocarcinomas focusing on the nature of the death in neoplastic cells and in infiltrating neutrophils. Adenocarcinoma cells, single or in small clusters, showed convoluted nuclei, irregularly condensed chromatin, loss of microvilli, and nuclear envelope dilatation.

Histologic coagulative tumour necrosis as a prognostic indicator of aggressiveness in renal, lung, thyroid and colorectal carcinomas: A brief review.

Tumour growth involves two essential deviations from the normal state including the induction of proliferative stimuli, and simultaneous suppression of potentially compensatory cell death. It has been suggested that the development of invasive cancer involves a progressive switch from predominantly apoptotic to necrotic tumour cell death. The presence of tumour necrosis in pathologic specimens may not only reflect tumour biology, but also provide additional beneficial prognostic information.

Ofatumumab, a fully human anti-CD20 monoclonal antibody, in biological-naive, rheumatoid arthritis patients with an inadequate response to methotrexate: a randomised, double-blind, placebo-controlled clinical trial.

Objectives: To evaluate the efficacy and safety of intravenous ofatumumab, a fully human anti-CD20 monoclonal antibody, in biological-naive, active rheumatoid arthritis (RA) patients despite methotrexate treatment.

Methods: In this double-blind, placebo-controlled, phase III study, active RA patients on stable methotrexate were randomly assigned to one course of two infusions of ofatumumab 700 mg (n=130) or placebo (n=130), 2 weeks apart. The primary endpoint was the ACR20 response at week 24.

Ultrastructural descriptions of heterotypic aggregation between eosinophils and tumor cells in human gastric carcinomas.

A histological variant of gastric adenocarcinoma, characterized by an intense tumor-associated tissue eosinophilia (TATE), has been occasionally reported in the literature. The purpose of this ultrastructural study was to determine the interactions between frequently occurring eosinophils and tumor cells in gastric carcinoma characterized by TATE. Fresh tumor tissue of 92 gastric carcinomas was processed for both light and electron microscopic examination.

Ultrastructural observations on inflammatory angiogenesis in gastric carcinomas with massive neutrophil infiltration.

Neutrophils are traditionally thought of as terminal effectors of inflammatory reaction, but experimental studies suggest that they play a direct role in the inflammatory angiogenesis of tumors. Thus, further evidence in humans is required regarding the mechanisms by which neutrophils induce tumor angiogenesis. In this study, 4 cases of human gastric carcinomas with massive neutrophil infiltration were studied by light and electron microscopy, focusing on the inflammatory angiogenesis in the tumor stroma.

High-efficiency gene transfer into nontransformed cells: utility for studying gene regulation and analysis of potential therapeutic targets.

The elucidation of the signalling pathways involved in inflammatory diseases, such as rheumatoid arthritis, could provide long sought after targets for therapeutic intervention. Gene regulation is complex and varies depending on the cell type, as well as the signal eliciting gene activation. However, cells from certain lineages, such as macrophages, are specialised to degrade exogenous material and consequently do not easily transfect.