RESUMEN
BACKGROUND: Disparities in social determinants of health have been linked to worse patient reported outcomes, higher pain, and increased risk of revision surgery following rotator cuff repair. Identification of perioperative predictors of increased healthcare utilization is of particular interest to surgeons to improve outcomes and mitigate the total cost of care. The effect of social deprivation on healthcare utilization has not been fully characterized. METHODS: This is a retrospective review of a single institution's experience with primary rotator cuff repair between 2012 and 2020. Demographic variables (age, race, gender, American Society of Anesthesiologists (ASA) score) and healthcare utilization (hospital readmission, emergency department visits, follow-up visits, telephone calls) were recorded within 90 days of surgery. The Area Deprivation Index (ADI) was recorded, and patients were separated into terciles according to their relative level of social deprivation. Outcomes were then stratified based on ADI tercile and compared. RESULTS: A total of 1695 patients were included. The upper, middle, and lower terciles of ADI consisted of 410, 767, and 518 patients, respectively. The most deprived tercile had greater emergency department visitation and office visitation within 90 days of surgery relative to the least and intermediate deprived terciles. Higher levels of social deprivation were independent risk factors for increased emergency department (ED) visitation and follow-up visitation. There was no difference in 90-day readmission rates or telephone calls made between the least, intermediate, and most deprived patients. CONCLUSIONS: Patients with higher levels of deprivation demonstrated greater postoperative hospital utilization. We hope to use these results to identify risk factors for increased hospital use, guide clinical decision making, increase transparency, and manage patient outcomes following rotator cuff repair surgery.
RESUMEN
Acute myeloid leukemia (AML) is a malignancy of immature myeloid blast cells with stem-like and chemoresistant cells being retained in the bone marrow through CXCL12-CXCR4 signaling. Current CXCR4 inhibitors mobilize AML cells into the bloodstream where they become more chemosensitive have failed to improve patient survival, likely reflecting persistent receptor localization on target cells. Here we characterize the signaling properties of CXCL12-locked dimer (CXCL12-LD), a bioengineered variant of the dimeric CXCL12 structure. CXCL12-LD binding resulted in lower levels of G protein, ß-arrestin, and intracellular calcium mobilization, consistent with the locked dimer being a partial agonist of CXCR4. Further, CXCL12-LD failed to induce chemotaxis in AML cells. Despite these partial agonist properties, CXCL12-LD increased CXCR4 internalization compared to wildtype and locked-monomer forms of CXCL12. Analysis of a previously published AML transcriptomic data showed CXCR4 positive AML cells co-express genes involved in chemoresistance and maintenance of a blast-like state. The CXCL12-LD partial agonist effectively mobilized stem cells into the bloodstream in mice suggesting a potential role for their use in targeting CXCR4. Together, our results suggest that enhanced internalization by CXCL12-LD partial agonist signaling can avoid pharmacodynamic tolerance and may identify new avenues to better target GPCRs.