Using Patient-Reported Outcomes Measurement Information System® (PROMIS) to Identify Physical and Psychosocial Quality of Life Issues in Lung Cancer Survivors.

Background: Lung cancer survivors (LCS) are living longer due to improved screening and treatment but often experience long-term treatment effects. Due to a traditionally poor prognosis, research related to LCS symptomology and associated quality of life (QOL) is lacking. Objective: The objective of this study was to develop a process for identifying symptomology and unmet needs affecting QOL in LCS. Methods: A literature review identified recommended methods of implementing a QOL screening program in LCS. Training guidelines using the best evidence were presented to the survivorship clinic (SC) staff. The Patient-Reported Outcomes Measurement Information System® (PROMIS-29) profile was used to collect data from LCS. The experience of the SC staff (N = 2) and providers (N = 2) in implementing the QOL screening program in LCS was assessed. Results: A 100% compliance rate in completing the PROMIS-29 profile was achieved. Physical function and pain interference were the most impacted QOL domains identified by LCS, while depression was the least. No challenges were identified in assisting LCS with profile completion. Providers agreed that the PROMIS-29 was instrumental in identifying QOL issues. Conclusion: A QOL screening program tailored to LCS-improved compliance and reliability in identifying QOL issues. Implications for Nursing: A QOL screening program using the PROMIS-29 may improve patient-provider interactions and value-based oncology care.

Mutational analysis of the enzymatic domain of Clostridium difficile toxin B reveals novel inhibitors of the wild-type toxin.

Toxin B (TcdB), a major Clostridium difficile virulence factor, glucosylates and inactivates the small GTP-binding proteins Rho, Rac, and Cdc42. In the present study we provide evidence that enzymatically inactive fragments of the TcdB enzymatic domain are effective intracellular inhibitors of native TcdB. Site-directed and deletion mutants of the TcdB enzymatic region (residues 1 to 556), lacking receptor binding and cell entry domains, were analyzed for attenuation of glucosyltransferase and glucosylhydrolase activity. Five of six derivatives from TcdB(1-556) were found to be devoid of enzymatic activity. In order to facilitate cell entry, mutants were genetically fused to lfn, which encodes the protective antigen binding region of anthrax toxin lethal factor and mediates the cell entry of heterologous proteins. In line with reduced enzymatic activity, the mutants also lacked cytotoxicity. Remarkably, pretreatment or cotreatment of cells with four of the mutants provided protection against the cytotoxic effects of native TcdB. Furthermore, a CHO cell line expressing enzymatically active TcdB(1-556) was also protected by the mutant-derived inhibitors, suggesting that inhibition occurred at an intracellular location. Protection also was afforded by the inhibitor to cells treated with Clostridium sordellii lethal toxin (TcsL), which uses the same cosubstrate as TcdB but shares Rac only as a common substrate target. Finally, the inhibitor did not provide protection against Clostridium novyi alpha-toxin (Tcnalpha), which shares similar substrates with TcdB yet uses a different cosubstrate. This is the first report to demonstrate that the potential exists to inhibit toxins at their intracellular site of action by using inactive mutants.