Ticagrelor Reduces Thromboinflammatory Markers in Patients With Pneumonia

Despite treatment advances for sepsis and pneumonia, significant improvements in outcome have not been realized. Antiplatelet therapy may improve outcome in pneumonia and sepsis. In this study, the authors show that ticagrelor reduced leukocytes with attached platelets as well as the inflammatory biomarker interleukin (IL)-6. Pneumonia patients receiving ticagrelor required less supplemental oxygen and lung function tests trended toward improvement. Disruption of the P2Y12 receptor in a murine model protected against inflammatory response, lung permeability, and mortality. Results indicate a mechanistic link between platelets, leukocytes, and lung injury in settings of pneumonia and sepsis, and suggest possible therapeutic approaches to reduce complications. (Targeting Platelet-Leukocyte Aggregates in Pneumonia With Ticagrelor [XANTHIPPE]; NCT01883869

Skeletal muscle munc18c and syntaxin 4 in human obesity

<p>Abstract</p> <p>Background</p> <p>Animal and cell culture data suggest a critical role for Munc18c and Syntaxin 4 proteins in insulin mediated glucose transport in skeletal muscle, but no studies have been published in humans.</p> <p>Methods</p> <p>We investigated the effect of a 12 vs. 48 hr fast on insulin action and skeletal muscle Munc18c and Syntaxin 4 protein in lean and obese subjects. Healthy lean (n = 14; age = 28.0 +/- 1.4 yr; BMI = 22.8 +/- 0.42 kg/m²) and obese subjects (n = 11; age = 34.6 +/- 2.3 yr; BMI = 36.1 +/- 1.5 kg/m²) were studied twice following a 12 and 48 hr fast. Skeletal muscle biopsies were obtained before a 3 hr 40 mU/m²/min hyperinsulinemic-euglycemic clamp with [6,6-²H₂]glucose infusion.</p> <p>Results</p> <p>Glucose rate of disappearance (Rd) during the clamp was lower in obese vs. lean subjects after the 12 hr fast (obese: 6.25 +/- 0.67 vs. lean: 9.42 +/- 1.1 mg/kgFFM/min, p = 0.007), and decreased significantly in both groups after the 48 hr fast (obese 3.49 +/- 0.31 vs. lean: 3.91 +/- 0.42 mg/kgFFM/min, p = 0.002). Munc18c content was not significantly different between lean and obese subjects after the 12 hour fast, and decreased after the 48 hr fast in both groups (p = 0.013). Syntaxin 4 content was not altered by obesity or fasting duration. There was a strong positive relationship between plasma glucose concentration and Munc18c content in lean and obese subjects during both 12 and 48 hr fasts (R²= 0.447, p = 0.0015). Significant negative relationships were also found between Munc18c and FFA (p = 0.041), beta-hydroxybutyrate (p = 0.039), and skeletal muscle AKT content (p = 0.035) in lean and obese subjects.</p> <p>Conclusion</p> <p>These data indicate Munc18c and Syntaxin 4 are present in human skeletal muscle. Munc18c content was not significantly different between lean and obese subjects, and is therefore unlikely to explain obesity-induced insulin resistance. Munc18c content decreased after prolonged fasting in lean and obese subjects concurrently with reduced insulin action. These data suggest changes in Munc18c content in skeletal muscle are associated with short-term changes in insulin action in humans.</p

An Opinion Paper of the Cardiology Practice and Research Network of the American College of Clinical Pharmacy: Recommendations for Training of Cardiovascular Pharmacy Specialists in Postgraduate Year 2 Residency Programs

Pharmacists in direct patient care settings are expanding their roles and responsibilities. These changes mandate a deeper and broader understanding of disease states, as well as influencing social, behavioral, and environmental factors. Existing guidelines and accreditation standards related to the training of graduate or cardiovascular pharmacist specialists (ie, Accreditation Council for Graduate Medical Education, American Society of Health‐System Pharmacists, American College of Clinical Pharmacy [ACCP]) provide some guidance on essential competencies. However, they stop short of providing recommendations for how to achieve all the objectives. The purpose of this paper is to build upon existing guidelines/standards, describing our recommendations for pharmacy residency training of a cardiovascular clinical specialist. The paper is broken down into the following sections: (1) Skills and Competencies (Building Clinical Skills, Application of Clinical Knowledge and Skills, Drug Information, Research and Scholarship, Teaching Skills, Interpersonal, Communication, and Presentation Skills), (2) Personal and Professional Growth (Growing Interpersonal Skills, Engaging with the Profession), (3) Program Design (Resident Selection, Preceptors and Mentoring, Expectations for Progress/Milestones, Program and Learning Experience Structure), and (4) Clinical and Therapeutic Content Expertise or Medical Knowledge. After each recommendation, specific details are provided to aid in conceptualizing how each can be achieved. Some recommendations are considered essential whereas others are designated as optional. This paper represents the opinion of the Cardiology Practice and Research Network of the American College of Clinical Pharmacy. It does not necessarily represent an official ACCP commentary, guideline, or statement of policy or position