Cancer cells have an efficient antioxidant system to counteract their increased generation of ROS. However, whether this ability to survive high levels of ROS has an important role in the growth and metastasis of tumors is not well understood. Here, we demonstrate that the redox protein thioredoxin-like 2 (TXNL2) regulates the growth and metastasis of human breast cancer cells through a redox signaling mechanism. TXNL2 was found to be overexpressed in human cancers, including breast cancers. Knockdown of TXNL2 in human breast cancer cell lines increased ROS levels and reduced NF-κB activity, resulting in inhibition of in vitro proliferation, survival, and invasion. In addition, TXNL2 knockdown inhibited tumorigenesis and metastasis of these cells upon transplantation into immunodeficient mice. Furthermore, analysis of primary breast cancer samples demonstrated that enhanced TXNL2 expression correlated with metastasis to the lung and brain and with decreased overall patient survival. Our studies provided insight into redox-based mechanisms underlying tumor growth and metastasis and suggest that TXNL2 could be a target for treatment of breast cancer.
The authors describe a quality improvement initiative aimed at decreasing unplanned 7- and 30-day readmission rates in an urban, pediatric, tertiary care hospital. A stepwise approach was used to disseminate the pilot initiative across 16 inpatient units. Use of a teach-back methodology combined with a discharge bundle resulted in an 8% reduction in 7-day readmission and 10% reduction in 30-day readmission over 16 months.
Colonoscopy with moderate sedation is a low-risk procedure, and the addition of EtCO2 did not improve safety or patient satisfaction but did increase cost. These data suggest that routine capnography in this setting may not be cost effective and that EtCO2 might be reserved for patients at higher risk of adverse events.
Background
Over 20 million invasive procedures are performed annually in the United States. The vast majority are performed with moderate sedation or deep sedation yet there is limited understanding of drivers of sedation quality and patient satisfaction. Currently, the major gap in quality assurance for invasive procedures is the lack of procedural sedation quality measures.
Objective
To develop and validate a robust, patient-centered measure of procedural sedation quality, the PROcedural Sedation Assessment Survey (PROSAS).
Design
Through a series of interviews with patients, proceduralists, nurses and anesthesiologists, and an interactive patient focus group, major domains influencing procedural sedation quality were used to create a multipart survey. The pilot survey was administered and revised in sequential cohorts of adults receiving moderate sedation for GI endoscopy. After revision, the PROSAS was administered to a validation cohort.
Setting
GI endoscopy unit.
Patients
A expert panel of proceduralists, nurses and anesthesiologists, an initial survey development cohort of 40 patients, and a validation cohort of 858 patients undergoing sedation for outpatient GI endoscopy with additional surveys completed by the gastroenterologist, procedure nurse and recovery nurse.
Main Outcomes and Measures
Survey characteristics of the PROSAS.
Results
Patients were able to independently complete the PROSAS after procedural sedation before discharge. 91.6% of patients reported minimal discomfort; however, 8.4% of patients reported significant discomfort and 2.4% of patients experienced hemodynamic and/or respiratory instability. There was a high correlation between patient reported intraprocedure discomfort and both clinician assessments of procedural discomfort and patient recall of procedural pain 24 to 48 hours postprocedure (p<0.001 for all), suggesting high external validity.
Limitations
Single-center study, variability of sedation technique between providers, inclusion of patients with chronic pain on analgesics
Conclusions
The PROSAS is a clinically relevant, patient-centered, easily administered instrument that allows for standardized evaluation of procedural sedation quality. The PROSAS may be useful in both research and clinical settings.
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