Outcomes of Immune Checkpoint Inhibitor Administration in Hospitalized Patients With Solid Tumor Malignancies.

PURPOSE: More oncologists desire to treat their patients with immune checkpoint inhibitors (ICIs) in the inpatient setting as their use has become more widespread for numerous oncologic indications. This is cost-prohibitive to patients and institutions because of high drug cost and lack of reimbursement in the inpatient setting. We sought to examine current practice of inpatient ICI administration to determine if and in which clinical scenarios it may provide significant clinical benefit and therefore be warranted regardless of cost. METHODS: We conducted a retrospective chart review of adult patients who received at least one dose of an ICI for treatment of an active solid tumor malignancy during hospitalization at a single academic medical center between January 2017 and June 2018. Patient, disease, and admission characteristics including mortality data were examined, and cost analysis was performed. RESULTS: Sixty-five doses of ICIs were administered to 58 patients during the study period. Nearly 40% and 80% of patients died within 30 days and 180 days of ICI administration, respectively. There was a trend toward longer overall survival in patients with good prognostic factors including positive programmed death-ligand 1 (PD-L1) expression or microsatellite instability-high (MSI-H) status. Slightly over 70% of patients were discharged within 7 days of ICI administration. The total cost of inpatient ICI administration over the 18-month study period was $615,016 US dollars. CONCLUSION: Inpatient ICI administration is associated with high costs and poor outcomes in acutely ill hospitalized patients with advanced solid tumor malignancies and therefore should largely be avoided. Careful discharge planning to expedite outpatient treatment after discharge will be paramount in ensuring patients with good prognostic features who will benefit most from ICI therapy can be promptly treated in the outpatient setting as treating very close to discharge in the inpatient setting appears to be unnecessary, regardless of tumor features.

Impact of Extended Duty Hours on Perceptions of Care and Objective Patient Outcomes.

OBJECTIVE: In 2017, interns were permitted to work continuously for up to 28 hours at a time, a reversal from the previously mandated 16-hour limit. Our objective was to evaluate perceptions of care and patient outcomes on an extended (28-hour) compared with a limited (16-hour) duty-hour system on identical interdisciplinary teams. METHODS: Sixty-two interns, 27 residents, 28 attendings, and 449 patients participated. Patients completed surveys assessing their satisfaction. Anonymous weekly surveys were obtained from interns, residents, and attendings evaluating perceptions of intern tiredness, overall satisfaction, and performance. Nursing surveys evaluated intern and medical team performance. Objective outcome measures, including intensive care unit transfers, length of stay, readmissions, mortality, and complications, were assessed through a retrospective, blinded chart review. RESULTS: Patients reported similar satisfaction in care. Extended duty-hour interns reported significantly decreased familiarity with their patients, decreased ability to conduct physical exams on new patients, increased tiredness, and decreased overall satisfaction. Residents overseeing extended-duty interns reported significantly decreased quality in intern presentations and overall quality of teaching, and increased perception of intern tiredness and increased incorrect orders. Attending physicians reported significantly improved quality of new patient presentations by extended duty-hour interns. No significant differences in patient objective outcome measures were noted. CONCLUSIONS: Extended intern duty hours do not affect patient's satisfaction with their care. Although interns in the extended duty-hour system reported significantly increased fatigue and decreased overall satisfaction and residents' perceived increases in incorrect intern orders in the extended duty-hour system, there were no detrimental effects on patient safety.

Protein triggered fluorescence switching of near-infrared emitting nanoparticles for contrast-enhanced imaging.

Sub-100 nm colloidal particles which are surface-functionalized with multiple environmentally-sensitive moieties have the potential to combine imaging, early detection, and the treatment of cancer with a single type of long-circulating "nanodevice". Deep tissue imaging is achievable through the development of particles which are surface-modified with fluorophores that operate in the near-infrared (NIR) spectrum and where the fluorophore's signal can be maximized by "turning-on" the fluorescence only in the targeted tissue. We present a general approach for the synthesis of NIR emitting nanoparticles that exhibit a protein triggered activation/deactivation of the emission. Dispersing the particles into an aqueous solution, such as phosphate buffered saline (PBS), resulted in an aggregation of the hydrophobic fluorophores and a cessation of emission. The emission can be reinstated, or activated, by the conversion of the surface-attached fluorophores from an aggregate to a monomeric species with the addition of an albumin. This activated probe can be deactivated and returned to a quenched state by a simple tryptic digestion of the albumin. The methodology for emission switching offers a path to maximize the signal from the typically weak quantum yield inherent in NIR fluorophores.