An Update on Monoclonal Antibody Therapy to Treat Moderate-to-Severe Asthma: Benefits, Choices, and Limitations.

Moderate or severe asthma is a complex disease process clinically manifesting as at least partially reversible airway obstruction due to airway hyperresponsiveness. Asthma therapy was based primarily on symptom control until recent studies of its mechanisms have led to a host of new targeted, safe, and effective therapies. These biologic therapies directly attack culprit inflammatory mediators at the molecular level. In this article we review currently available biologic agents for the treatment of moderate-to-severe asthma. We provide information deemed necessary to optimally consult with an asthma specialist to choose, assist in financial arrangements for, and coordinate the use of these new, promising, Food and Drug Administration-approved biologic agents. We will also briefly review the molecular pathways targeted with each class of biologic to provide a more in-depth understanding of why these targeted therapies are effective. These biologics are the first of many to come that modify newly discovered components of the immune system with which many physicians are unfamiliar.

NephCure Accelerating Cures Institute: A Multidisciplinary Consortium to Improve Care for Nephrotic Syndrome.

INTRODUCTION: NephCure Accelerating Cures Institute (NACI) is a collaborative organization sponsored by NephCure Kidney International and the University of Michigan. The Institute is composed of 7 cores designed to improve treatment options and outcomes for patients with glomerular disease: Clinical Trials Network, Data Warehouse, Patient-Reported Outcomes (PRO) and Endpoints Consortium, Clinical Trials Consulting Team, Quality Initiatives, Education and Engagement, and Data Coordinating Center. METHODS: The Trials Network includes 22 community- and hospital-based nephrology practices, 14 of which are trial-only sites. Eight sites participate in the NACI Registry, and as of October 2017, 1054 patients are enrolled with diagnoses including but not limited to focal segmental glomerulosclerosis, minimal change disease, membranous nephropathy, IgA nephropathy, and childhood-onset nephrotic syndrome. By using electronic health record data extraction, robust and efficient clinical data are captured while minimizing the burden to site-based network staff. RESULTS: The Data Warehouse includes her-extracted data from registry patients, PRO development data, and data from completed observational studies and clinical trials. The Clinical Trial Consulting Team provides support for trial design in rare diseases leveraging these data. The PRO and Endpoints Consortium develops shorter-term endpoints while capturing the patient-reported significance of interventions under study. The Quality Initiatives and Education/Engagement cores elevate the level of care for patients. The Data Coordinating Center manages the analysis and operations of the Institute. CONCLUSION: By engaging with patients, academia, industry, and patient advocate community representatives, including our Patient Advisory Board, NACI strives for better outcomes and treatments using evidence-based support for clinical trial design.

Molecular mechanisms and cell signaling of 20-hydroxyeicosatetraenoic acid in vascular pathophysiology.

Cytochrome P450s enzymes catalyze the metabolism of arachidonic acid to epoxyeicosatrienoic acids (EETs), dihydroxyeicosatetraenoic acid and hydroxyeicosatetraeonic acid (HETEs). 20-HETE is a vasoconstrictor that depolarizes vascular smooth muscle cells by blocking K+ channels. EETs serve as endothelial derived hyperpolarizing factors. Inhibition of the formation of 20-HETE impairs the myogenic response and autoregulation of renal and cerebral blood flow. Changes in the formation of EETs and 20-HETE have been reported in hypertension and drugs that target these pathways alter blood pressure in animal models. Sequence variants in CYP4A11 and CYP4F2 that produce 20-HETE, UDP-glucuronosyl transferase involved in the biotransformation of 20-HETE and soluble epoxide hydrolase that inactivates EETs are associated with hypertension in human studies. 20-HETE contributes to the regulation of vascular hypertrophy, restenosis, angiogenesis and inflammation. It also promotes endothelial dysfunction and contributes to cerebral vasospasm and ischemia-reperfusion injury in the brain, kidney and heart. This review will focus on the role of 20-HETE in vascular dysfunction, inflammation, ischemic and hemorrhagic stroke and cardiac and renal ischemia reperfusion injury.

Labile hypertension: characteristics of a referred cohort.

From 88 subjects with labile high blood pressure (LHBP), we collected blood pressure variability (BPV) and assessed relationships with age, medications, and nocturnal pattern via ambulatory blood pressure monitoring. The average age of the subjects was 64 ± 13 years and they were on 1.5 ± 1.3 antihypertensives. BPV did not differ diurnally and was not influenced by medication. Aging associates with increasing daytime systolic but not diastolic BPV, with increasing nighttime systolic BP, and decreasing diastolic BP diurnally. Subjects had widened pulse pressure and abnormal diurnal pattern with age. Further studies are needed to stratify an individual's risk associated with LHBP.