Barriers to Early Hospital Discharge: A Cross-Sectional Study at Five Academic Hospitals.

BACKGROUND: Understanding the issues delaying hospital discharges may inform efforts to improve hospital throughput. OBJECTIVE: This study was conducted to identify and determine the frequency of barriers contributing to delays in placing discharge orders. DESIGN: This was a prospective, cross-sectional study. Physicians were surveyed at approximately 8:00 AM, 12:00 PM, and 3:00 PM and were asked to identify patients that were "definite" or "possible" discharges and to describe the specific barriers to writing discharge orders. SETTING: This study was conducted at five hospitals in the United States. PARTICIPANTS: The study participants were attending and housestaff physicians on general medicine services. PRIMARY OUTCOMES AND MEASURES: Specific barriers to writing discharge orders were the primary outcomes; the secondary outcomes included discharge order time for high versus low team census, teaching versus nonteaching services, and rounding style. RESULTS: Among 1,584 patient evaluations, the most common delays for patients identified as "definite" discharges (n = 949) were related to caring for other patients on the team or waiting to staff patients with attendings. The most common barriers for patients identified as "possible" discharges (n = 1,237) were awaiting patient improvement and for ancillary services to complete care. Discharge orders were written a median of 43-58 minutes earlier for patients on teams with a smaller versus larger census, on nonteaching versus teaching services, and when rounding on patients likely to be discharged first (all P < .003). CONCLUSIONS: Discharge orders for patients ready for discharge are most commonly delayed because physicians are caring for other patients. Discharges of patients awaiting care completion are most commonly delayed because of imbalances between availability and demand for ancillary services. Team census, rounding style, and teaching teams affect discharge times.

Val-boroPro accelerates T cell priming via modulation of dendritic cell trafficking resulting in complete regression of established murine tumors.

Although tumors naturally prime adaptive immune responses, tolerance may limit the capacity to control progression and can compromise effectiveness of immune-based therapies for cancer. Post-proline cleaving enzymes (PPCE) modulate protein function through N-terminal dipeptide cleavage and inhibition of these enzymes has been shown to have anti-tumor activity. We investigated the mechanism by which Val-boroPro, a boronic dipeptide that inhibits post-proline cleaving enzymes, mediates tumor regression and tested whether this agent could serve as a novel immune adjuvant to dendritic cell vaccines in two different murine syngeneic murine tumors. In mice challenged with MB49, which expresses the HY antigen complex, T cell responses primed by the tumor with and without Val-boroPro were measured using interferon gamma ELISPOT. Antibody depletion and gene-deficient mice were used to establish the immune cell subsets required for tumor regression. We demonstrate that Val-boroPro mediates tumor eradication by accelerating the expansion of tumor-specific T cells. Interestingly, T cells primed by tumor during Val-boroPro treatment demonstrate increased capacity to reject tumors following adoptive transfer without further treatment of the recipient. Val-boroPro -mediated tumor regression requires dendritic cells and is associated with enhanced trafficking of dendritic cells to tumor draining lymph nodes. Finally, dendritic cell vaccination combined with Val-boroPro treatment results in complete regression of established tumors. Our findings demonstrate that Val-boroPro has antitumor activity and a novel mechanism of action that involves more robust DC trafficking with earlier priming of T cells. Finally, we show that Val-boroPro has potent adjuvant properties resulting in an effective therapeutic vaccine.

Radiofrequency ablation induces antigen-presenting cell infiltration and amplification of weak tumor-induced immunity.

PURPOSE: To evaluate the influence of subtotal radiofrequency (RF) ablation on a tumor-specific immune response in a murine tumor model and to explore the role of intratumoral dendritic cells (ITDCs) in mediating this effect. MATERIALS AND METHODS: Animal work was performed according to an approved protocol and in compliance with the National Cancer Institute Animal Care and Use Committee guidelines and regulations. A murine urothelial carcinoma (MB49) model expressing the male minor histocompatibility (HY) antigen was inoculated subcutaneously in female mice. Fourteen days later, splenic T cells were analyzed with enzyme-linked immunosorbent spot for HY immune response (n = 57). In subsequent experiments, mice were randomized into control (n = 7), RF ablation, ITDC (n = 9), and RF ablation + ITDC (n = 9) groups and monitored for tumor growth. Eleven days after treatment, tumors were harvested for histologic and immunohistochemical analysis. Animals demonstrating complete tumor regression were rechallenged in the contralateral flank. RESULTS: Animals treated with subtotal RF ablation showed significant increases in tumor-specific class I and II responses to HY antigens and tumor regression. RF ablation, ITDC, and combined groups demonstrated similar levels of antigen-presenting cell infiltration; all groups demonstrated greater levels of infiltration compared with untreated controls. ITDC injection also resulted in tumor regression. However, combination therapy did not enhance tumor regression when compared with either treatment alone. Rechallenged mice in RF ablation, ITDC, and combination groups demonstrated significant tumor growth inhibition compared with controls. CONCLUSION: Subtotal RF ablation treatment results in enhanced systemic antitumor T-cell immune responses and tumor regression that is associated with increased dendritic cell infiltration. ITDC injection mimics the RF ablation effect but does not increase immune responses when injected immediately after RF ablation.