Osteopontin (OPN) plays an important functional role in both physiologic and pathologic states. OPN is implicated in the progression of fibrosis, cancer, and metastatic disease in several organ systems. The epithelial-mesenchymal transition (EMT), first described in embryology, is increasingly being recognized as a significant contributor to fibrotic phenotypes and tumor progression. Several well-established transcription factors regulate EMT and are conserved across tissue types and organ systems, including TWIST, zinc finger E-box-binding homeobox (ZEB), and SNAIL-family members. Recent literature points to an important relationship between OPN and EMT, implicating OPN as a key regulatory component of EMT programs. In this review, OPN’s interplay with traditional EMT activators, both directly and indirectly, will be discussed. Also, OPN’s ability to restructure the tissue and tumor microenvironment to indirectly modify EMT will be reviewed. Together, these diverse pathways demonstrate that OPN is able to modulate EMT and provide new targets for directing therapeutics.

The epithelial to mesenchymal transition (EMT) is implicated in many processes, ranging from tissue and organogenesis to cancer and metastatic spread. Understanding the key regulatory mechanisms and mediators within this process offers the opportunity to develop novel therapeutics with broad clinical applicability. To date, several components of EMT already are targeted using pharmacologic agents in fibrosis and cancer. As our knowledge of EMT continues to grow, the potential for novel therapeutics will also increase. This review focuses on the role of EMT both as a necessary part of development and a key player in disease progression, specifically the similarity in pathways used during both processes as targets for drug development. Also, the key role of the tumor microenvironment with EMT is outlined, focusing on both co‐factors and cell types with the ability to modulate the progression of EMT in cancer and metastatic disease. Lastly, we discuss the current status of clinical therapies both in development and those progressed to clinical trial specifically targeting pathologic EMTs including small molecule inhibitors, non‐coding RNAs, exogenous co‐factors, and adjunctive therapies to current chemotherapeutics.

BACKGROUND: Post-discharge surgical care fragmentation is defined as readmission to any hospital other than the hospital at which surgery was performed. The objective of this study was to assess the impact of fragmented readmissions within the first year after orthotopic liver transplantation (OLT). STUDY DESIGN: The Healthcare Cost and Utilization Project State Inpatient Databases for Florida and California from 2006 to 2011 were used to identify OLT patients. Post-discharge fragmentation was defined as any readmission to a non-index hospital, including readmitted patients transferred to the index hospital after 24 hours. Outcomes included adverse events, defined as 30-day mortality and 30-day readmission after a fragmented readmission. All statistical analyses considered a hierarchical data structure and were performed with multilevel, mixed-effects models. RESULTS: We analyzed 2,996 patients with 7,485 readmission encounters at 299 hospitals; 1,236 (16.5%) readmissions were fragmented. After adjustment for age, sex, readmission reason, index liver transplantation cost, readmission length of stay, number of previous readmissions, and time from transplantation, post-discharge fragmentation increased the odds of both 30-day mortality (odds ratio [OR] = 1.75; 95% CI 1.16 to 2.65) and 30-day readmission (OR = 2.14; 95% CI 1.83 to 2.49). Predictors of adverse events after a fragmented readmission included increased number of previous readmissions (OR = 1.07; 95% CI 1.01 to 1.14) and readmission within 90 days of OLT (OR = 2.19; 95% CI 1.61 to 2.98). CONCLUSIONS: Post-discharge fragmentation significantly increases the risk of both 30-day mortality and subsequent readmission after a readmission in the first year after OLT. More inpatient visits before a readmission and less time elapsed from index surgery increase the odds of an adverse event after discharge from a fragmented readmission. These parameters could guide transfer decisions for patients with post-discharge fragmentation.