Study design and baseline profile for adults with type 2 diabetes in the once-weekly subcutaneous SEmaglutide randomized PRAgmatic (SEPRA) trial.

Introduction: Once-weekly subcutaneous semaglutide, a glucagon-like peptide-1 analog, is approved in the USA as an adjunct to diet and exercise for adults with inadequately controlled type 2 diabetes (T2D) to improve glycemic control and reduce the risk of major adverse cardiovascular events in people with T2D and established cardiovascular disease. The Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN) phase III clinical trial program demonstrated the efficacy and safety of once-weekly subcutaneous semaglutide; however, determining its effectiveness in a real-world setting could support decision-making by clinicians, payers and policy makers in routine clinical practice.

Research Design And Methods: SEmaglutide PRAgmatic (SEPRA) is an ongoing open-label, randomized, pragmatic clinical trial designed to compare the effects of once-weekly subcutaneous semaglutide versus standard of care in US health-insured adults with T2D and physician-determined inadequate glycemic control.

Sustained Remission and Outcomes with Abatacept plus Methotrexate Following Stepwise Dose De-escalation in Patients with Early Rheumatoid Arthritis.

Introduction: One target of rheumatoid arthritis (RA) treatment is to achieve early sustained remission; over the long term, patients in sustained remission have less structural joint damage and physical disability. We evaluated Simplified Disease Activity Index (SDAI) remission with abatacept + methotrexate versus abatacept placebo + methotrexate and impact of de-escalation (DE) in anti-citrullinated protein antibody (ACPA)-positive patients with early RA.

Methods: The phase IIIb, randomized, AVERT-2 two-stage study (NCT02504268) evaluated weekly abatacept + methotrexate versus abatacept placebo + methotrexate.

The value of imaging and clinical outcomes in a phase II clinical trial of a lysophosphatidic acid receptor antagonist in idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease characterized by worsening dyspnea and lung function and has a median survival of 2-3 years. Forced vital capacity (FVC) is the primary endpoint used most commonly in IPF clinical trials as it is the best surrogate for mortality. This study assessed quantitative scores from high-resolution computed tomography (HRCT) developed by machine learning as a secondary efficacy endpoint in a 26-week phase II study of BMS-986020 - an LPA receptor antagonist - in patients with IPF.

Safety of Abatacept Versus Placebo in Rheumatoid Arthritis: Integrated Data Analysis of Nine Clinical Trials.

Objective: To assess the safety of abatacept treatment in rheumatoid arthritis (RA) using integrated data from multiple clinical trials.

Methods: Data from nine double-blind, placebo-controlled studies of abatacept treatment (seven intravenous, two subcutaneous) in patients with RA were pooled, focusing on safety events in the double-blind treatment period of each study. Incidence rates (IRs) of adverse events (AEs) per 100 patient-years of exposure were calculated for abatacept- and placebo-treated patients.

Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial of BMS-986020, a Lysophosphatidic Acid Receptor Antagonist for the Treatment of Idiopathic Pulmonary Fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) causes irreversible loss of lung function. The lysophosphatidic acid receptor 1 (LPA) pathway is implicated in IPF etiology. Safety and efficacy of BMS-986020, a high-affinity LPA antagonist, was assessed vs placebo in a phase 2 study in patients with IPF.

Assessment of atherosclerosis in chronic granulomatous disease.

Background: Patients with chronic granulomatous disease (CGD) experience immunodeficiency because of defects in the phagocyte NADPH oxidase and the concomitant reduction in reactive oxygen intermediates. This may result in a reduction in atherosclerotic injury.

Methods And Results: We prospectively assessed the prevalence of cardiovascular risk factors, biomarkers of inflammation and neutrophil activation, and the presence of magnetic resonance imaging and computed tomography quantified subclinical atherosclerosis in the carotid and coronary arteries of 41 patients with CGD and 25 healthy controls in the same age range.

MicroRNA expression altered by diet: can food be medicinal?

As the link between metabolism and major disease processes becomes more well-defined, the identification of key molecular targets is leading to new therapeutic strategies. As a result, small non-coding RNA molecules that regulate gene expression via epigenetic alterations, microRNAs have been identified as regulators of these metabolic processes. In the last decade, dietary interventions have been used to change metabolism and to potentially alter disease progression and clinical outcomes.

Cellular stress induced alterations in microRNA let-7a and let-7b expression are dependent on p53.

Genotoxic stressors, such as radiation, induce cellular damage that activates pre-programmed repair pathways, some of which involve microRNAs (miRNA) that alter gene expression. The let-7 family of miRNA regulates multiple cellular processes including cell division and DNA repair pathways. However, the role and mechanism underlying regulation of let-7 genes in response to stress have yet to be elucidated.

Residual NADPH oxidase and survival in chronic granulomatous disease.

Background: Failure to generate phagocyte-derived superoxide and related reactive oxygen intermediates (ROIs) is the major defect in chronic granulomatous disease, causing recurrent infections and granulomatous complications. Chronic granulomatous disease is caused by missense, nonsense, frameshift, splice, or deletion mutations in the genes for p22(phox), p40(phox), p47(phox), p67(phox) (autosomal chronic granulomatous disease), or gp91(phox) (X-linked chronic granulomatous disease), which result in variable production of neutrophil-derived ROIs. We hypothesized that residual ROI production might be linked to survival in patients with chronic granulomatous disease.

Loratadine dysregulates cell cycle progression and enhances the effect of radiation in human tumor cell lines.

Background: The histamine receptor-1 (H1)-antagonist, loratadine has been shown to inhibit growth of human colon cancer xenografts in part due to cell cycle arrest in G2/M. Since this is a radiation sensitive phase of the cell cycle, we sought to determine if loratadine modifies radiosensitivity in several human tumor cell lines with emphasis on human colon carcinoma (HT29).

Methods: Cells were treated with several doses of loratadine at several time points before and after exposure to radiation.

Ionizing radiation-induced oxidative stress alters miRNA expression.

Background: MicroRNAs (miRNAs) are small, highly conserved, non-coding RNA that alter protein expression and regulate multiple intracellular processes, including those involved in the response to cellular stress. Alterations in miRNA expression may occur following exposure to several stress-inducing anticancer agents including ionizing radiation, etoposide, and hydrogen peroxide (H(2)O(2)).

Methodology/principal Findings: Normal human fibroblasts were exposed to radiation, H(2)O(2), or etoposide at doses determined by clonogenic cell survival curves.

Hypokalemic Periodic Paralysis: a case report and review of the literature.

Hypokalemic Periodic Paralysis is one form of Periodic Paralysis, a rare group of disorders that can cause of sudden onset weakness. A case of a 29 year old male is presented here. The patient presented with sudden onset paralysis of his extremities.

Pretreatment predictors of death from other causes in men with prostate cancer.

Purpose: Most men diagnosed with prostate cancer will die of other causes and pretreatment patient characteristics may identify those who are likely to die of other causes. Accurate stratification of patients by risk of other cause mortality may reduce needless treatment preventing morbidity and expense.

Materials And Methods: Using the CaPSURE database a cohort of men was identified with clinically localized prostate cancer who had definitive treatment with radical prostatectomy or radiation therapy between 1995 and 2004.

Assessment of tissue redox status using metabolic responsive contrast agents and magnetic resonance imaging.

Regulation of tissue redox status is important to maintain normal physiological conditions in the living body. Disruption of redox homoeostasis may lead to oxidative stress and can induce many pathological conditions such as cancer, neurological disorders and ageing. Therefore, imaging of tissue redox status could have clinical applications.

Intrarectal amifostine during external beam radiation therapy for prostate cancer produces significant improvements in Quality of Life measured by EPIC score.

Purpose: To test whether intrarectal amifostine limits symptoms of radiation proctitis, measured by using the Radiation Therapy Oncology Group (RTOG) gastrointestinal (GI) toxicity score and the Expanded Prostate Cancer Index Composite (EPIC) score.

Methods And Materials: Patients with localized prostate cancer received amifostine as a rectal suspension 30-45 minutes before daily three-dimensional conformal radiation therapy. The first 18 patients received 1 g of amifostine, and the next 12 patients received 2 g.

Effects of gamma radiation on FcepsilonRI and TLR-mediated mast cell activation.

Ionizing gamma radiation has several therapeutic indications including bone marrow transplantation and tumor ablation. Among immune cells, susceptibility of lymphocytes to gamma radiation is well known. However, there is little information on the effects of gamma radiation on mast cells, which are important in both innate and acquired immunity.

Therapeutic and clinical applications of nitroxide compounds.

Nitroxide compounds have been used for many years as biophysical tools, but only during the past 15-20 years have the many interesting biochemical interactions been discovered and harnessed for therapeutic applications. By modifying oxidative stress and altering the redox status of tissues, nitroxides have the ability to interact with and alter many metabolic processes. This interaction can be exploited for therapeutic and research use, including protection against ionizing radiation, as probes in functional magnetic resonance imaging, cancer prevention and treatment, control of hypertension and weight, and protection from damage resulting from ischemia/reperfusion injury.

Oral pirfenidone in patients with chronic fibrosis resulting from radiotherapy: a pilot study.

Background: Fibrosis is a common side effect after treatment with ionizing radiation. Several methods to ameliorate debilitating fibrosis have been employed but without consistent results. The goal of this pilot study is to determine if Pirfenidone, a novel regulator of cytokine gene expression, has the potential to ameliorate established radiation-induced fibrosis.

The chemistry and biology of nitroxide compounds.

Cyclic nitroxides are a diverse group range of stable free radicals that have unique antioxidant properties. Because of their ability to interact with free radicals, they have been used for many years as biophysical tools. During the past 15-20 years, however, many interesting biochemical interactions have been discovered and harnessed for therapeutic applications.