Factors associated with unplanned transfers among cancer patients at a freestanding acute rehabilitation facility.

BACKGROUND: Cancer patients undergoing inpatient rehabilitation often have high risk of complications leading to unplanned transfer to acute care. Prior studies have identified factors associated with these transfers but have been limited to examining factors that pertain to initial admission to rehabilitation and were not conducted in a freestanding inpatient rehabilitation facility. OBJECTIVE: The study aimed to include these prerehabilitation factors in addition to factors upon initial assessment in rehabilitation. It was hypothesized that specific factors from each of these periods would be associated with unplanned transfer to acute care. DESIGN: Retrospective cohort study. SETTING: Freestanding academic inpatient rehabilitation facility affiliated with an academic tertiary care facility with a comprehensive cancer center. PATIENTS: Retrospective review of 330 specific encounters unique to 250 patients from March 2017 to September 2018. MAIN OUTCOME MEASURES: The outcome measure was unplanned transfer to acute care. A binary logistic regression model was used to examine the relationship between factors from oncologic history, acute care course, and factors upon admission to rehabilitation to unplanned transfer to acute care. RESULTS: From 330 encounters, there were 111 unplanned transfers (34%). Unplanned transfer to acute care was independently associated with gastrointestinal malignancy (odds ratio [OR] 4.4, p = .01), 6-minute walk test less than 90 m (OR 4.6, p = .003), and prior unplanned transfer (OR 3.5, p = .007). CONCLUSIONS: The study suggests that oncologic and functional prerehabilitation markers are associated with an increased likelihood of unplanned transfer during inpatient cancer rehabilitation. These findings will provide a framework for creating predictive tools for unplanned transfers in cancer rehabilitation patients.

Pancreatic Cancer Cell Migration and Metastasis Is Regulated by Chemokine-Biased Agonism and Bioenergetic Signaling.

Patients with pancreatic ductal adenocarcinoma (PDAC) invariably succumb to metastatic disease, but the underlying mechanisms that regulate PDAC cell movement and metastasis remain little understood. In this study, we investigated the effects of the chemokine gene CXCL12, which is silenced in PDAC tumors, yet is sufficient to suppress growth and metastasis when re-expressed. Chemokines like CXCL12 regulate cell movement in a biphasic pattern, with peak migration typically in the low nanomolar concentration range. Herein, we tested the hypothesis that the biphasic cell migration pattern induced by CXCL12 reflected a biased agonist bioenergetic signaling that might be exploited to interfere with PDAC metastasis. In human and murine PDAC cell models, we observed that nonmigratory doses of CXCL12 were sufficient to decrease oxidative phosphorylation and glycolytic capacity and to increase levels of phosphorylated forms of the master metabolic kinase AMPK. Those same doses of CXCL12 locked myosin light chain into a phosphorylated state, thereby decreasing F-actin polymerization and preventing cell migration in a manner dependent upon AMPK and the calcium-dependent kinase CAMKII. Notably, at elevated concentrations of CXCL12 that were insufficient to trigger chemotaxis of PDAC cells, AMPK blockade resulted in increased cell movement. In two preclinical mouse models of PDAC, administration of CXCL12 decreased tumor dissemination, supporting our hypothesis that chemokine-biased agonist signaling may offer a useful therapeutic strategy. Our results offer a mechanistic rationale for further investigation of CXCL12 as a potential therapy to prevent or treat PDAC metastasis.