Receptor-independent, direct membrane binding leads to cell-surface lipid sorting and Syk kinase activation in dendritic cells.

Binding of particulate antigens by antigen-presenting cells is a critical step in immune activation. Previously, we demonstrated that uric acid crystals are potent adjuvants, initiating a robust adaptive immune response. However, the mechanisms of activation are unknown. By using atomic force microscopy as a tool for real-time single-cell activation analysis, we report that uric acid crystals could directly engage cellular membranes, particularly the cholesterol components, with a force substantially stronger than protein-based cellular contacts. Binding of particulate substances activated Syk kinase-dependent signaling in dendritic cells. These observations suggest a mechanism whereby immune cell activation can be triggered by solid structures via membrane lipid alteration without the requirement for specific cell-surface receptors, and a testable hypothesis for crystal-associated arthropathies, inflammation, and adjuvanticity.

Angina and associated healthcare costs following percutaneous coronary intervention: A real-world analysis from a multi-payer database.

OBJECTIVES: To study the contemporary, real-world clinical and economic burden associated with angina after percutaneous coronary intervention (PCI). BACKGROUND: Angina adversely affects quality of life and medical costs, yet data on real-world prevalence of angina following PCI and its associated economic consequences are limited. METHODS: In a multi-payer administrative claims database, we identified adults with incident inpatient PCI admissions between 2008 and 2011 who had at least 12 months of continuous medical and pharmacy benefits before and after the procedure. Patients were followed for up to 36 months. Using claims, we ascertained post-PCI outcomes: angina or chest pain, acute myocardial infarction, acute coronary syndrome, repeat PCI, healthcare service utilization, and costs. RESULTS: Among 51,710 study patients (mean age 61.8, 72% male), post-PCI angina or chest pain was present in 28% by 12 months and 40% by 36 months. Compared with patients who did not experience chest pain, angina or ACS, total healthcare costs in the first year after the index PCI were 1.8 times greater for patients with angina or chest pain ($32,437 vs. $17,913, P < 0.001). These cost differentials continued to 36 months. CONCLUSIONS: Angina after PCI is a frequent and expensive outcome. Further research is needed to identify risk factors and potentially improve outcomes for post-PCI angina. © 2016 Wiley Periodicals, Inc.

Paraduodenal pancreatitis as an uncommon cause of gastric outlet obstruction: A case report and review of the literature.

INTRODUCTION: Paraduodenal pancreatitis (PP) is an under-recognized form of focal chronic or recurrent pancreatitis. Since PP presents with non-specific symptoms and shares radiological and histopathological features with other entities, it can be challenging to diagnose. PRESENTATION OF CASE REPORT: Herein, a case of a 64 year-old Caucasian male with PP presenting with recurrent gastric outlet obstruction (GOO) is detailed. Over the course of two years, he underwent multiple balloon dilatations for symptom management. His diagnostic course was complicated by inconclusive and misleading biopsies. CONCLUSION: PP can rarely present as GOO in otherwise asymptomatic patients. A preoperative pathologic diagnosis can be difficult to obtain, and in this case delayed definitive surgical management. The case is discussed in detail, and a concise review the current literature was undertaken.

Adenosine deamination sustains dendritic cell activation in inflammation.

Adenosine is a suppressive agent that protects the host from excessive tissue injury associated with strong inflammation. In tissue stress, higher levels of adenosine signal through adenosine receptors to exert strong anti-inflammatory effects, and thus protect host cells. Existing evidence also suggests that elevated adenosine potently down-regulates the activation of lymphocytes during inflammation. This notion, however, is in contrast with another basic observation that the immune system is highly activated precisely under the same circumstances against pathogens. In this study, we show that inflammatory responses of dendritic cells (DCs) are highly sensitive to adenosine suppression. However, they intrinsically carry high adenosine deaminase activity, which in turn degrades and removes adenosine from the surroundings, cutting off DCs from the suppression. This regulatory mechanism is important in DC responses to pathogen-associated molecular patterns and their activation of T cells. Our findings suggest a mechanism that DCs maintain their hyperreactive state in inflammation despite the general state of suppression, and reveal a regulatory role of adenosine deaminase in DC innate immune responses.