PFKFB3 controls acinar IP3R-mediated Ca2+ overload to regulate acute pancreatitis severity.

Acute pancreatitis (AP) is among the most common hospital gastrointestinal diagnoses; understanding the mechanisms underlying the severity of AP is critical for development of new treatment options for this disease. Here, we evaluate the biological function of phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) in AP pathogenesis in 2 independent genetically engineered mouse models of AP. PFKFB3 was elevated in AP and severe AP (SAP), and KO of Pfkfb3 abrogated the severity of alcoholic SAP (FAEE-SAP). Using a combination of genetic, pharmacological, and molecular studies, we defined the interaction of PFKFB3 with inositol 1,4,5-trisphosphate receptor (IP3R) as a key event mediating this phenomenon. Further analysis demonstrated that the interaction between PFKFB3 and IP3R promotes FAEE-SAP severity by altering intracellular calcium homeostasis in acinar cells. Together, our results support a PFKFB3-driven mechanism controlling AP pathobiology and define this enzyme as a therapeutic target to ameliorate the severity of this condition.

Review of antibody-based immunotherapy in the treatment of non-Hodgkin lymphoma and patterns of use.

The creation of new cancer immunotherapies represents 1 of the most exciting advances taking place this decade. Although clinical studies continue to indicate improvement in clinical outcomes, the speed of its diffusion into actual practice is not known. It is important to understand practice variation in the use of recommended immunotherapies as new and more effective immunotherapies are developed. Additionally, as the field continues to grow, immunotherapy will encounter new barriers that will hinder its rapid adoption into clinical practice. This review aims to present a brief summary of the mechanisms and uses of antibody-based immunotherapies used to treat lymphoma and to present available practice variation data, including factors associated with variation. Review of the available data implicated patient characteristics and health care systems as being associated with practice variation; however, in several instances, ease of use, cost, toxicity, and physician knowledge contributed to variation, regardless of efficacy. As new immunotherapies are developed, these factors must be considered to increase the rapid diffusion of effective immunotherapies into wide clinical use.

Insights on practice variations in the management of lymphoma and leukemia.

Clinical practice guidelines are systematically developed statements designed to assist practitioners in making decisions about appropriate healthcare for specific clinical circumstances. Their successful implementation should improve quality of care by decreasing inappropriate variation and expediting the application of effective advances to everyday practice. Despite wide promulgation, guidelines have had limited effect on changing physician behaviors. This two-part review article highlights variations in the current recommended management of lymphoma (Part I) and leukemia (Part II), with some focus on targeted therapies. Focus on variations that may be amenable to educational programs designed for physicians were also considered in the review. For the purpose of this report, "variation" is defined as any deviation in the treatment or management of a particular hematologic malignancy where practice guidelines exist. Specific studies that demonstrate factors that may cause variations in clinical outcomes of hematologic malignancies and may contribute to variations in practice are featured.