Evaluation of Agreement Among Frailty Assessment Tools in Head and Neck Surgery.

OBJECTIVE: To evaluate intertest agreement among hand grip strength (HGS), the modified Frailty Index (mFI), and the Edmonton Frail Scale (EFS) in patients presenting for presurgical assessment in a head and neck surgery clinic. STUDY DESIGN: Prospective observational study. SETTING: Academic tertiary medical center. METHODS: Prospective data relating to 3 frailty measurements were collected for 96 consecutive adults presenting for presurgical counseling at a single high-volume head and neck surgical oncology clinic. Frailty was determined with previously validated thresholds for the mFI (≥3) and EFS (>7). The highest of 2 HGS measurements performed for the dominant hand was used to determine frail status based on previously validated sex- and body mass index-specific thresholds. Baseline characteristics were identified to determine the association of such variables to each tool. Agreement among frailty assessment tools was examined. RESULTS: The frequency of frailty in the cohort varied among tools, ranging from 29.2% (28/96) for HGS to 12.5% (12/96) for the mFI and 4.2% (4/96) for the EFS. The overall agreement among the 3 frailty tools via the Fleiss index was poor (kappa, 0.088; 95% CI, -0.028 to 0.203). CONCLUSION: Assessment of frailty is complex, and established frailty assessment tools may not agree on which patients are frail. When assessing a patient as frail, clinicians must be vigilant to the influence of frailty assessment tools on such determinations, which may contribute critical input during shared decision making for patients considering head and neck surgery or nonsurgical alternatives.

Chip-based analysis of protein-protein interactions by fluorescence detection and on-chip immunoprecipitation combined with microLC-MS/MS analysis.

A new chip-based method to identify protein-protein interactions was developed using the guanine nucleotide exchange factor GRF2 and two interacting proteins, Ras and calmodulin, as model proteins. A generic immobilization strategy for FLAG-tagged bait proteins on a protein-repellent streptavidin chip surface was implemented by presentation of an oriented anti-FLAG antibody. A flow cell device, integrating different chip surfaces, was developed, and the interaction of immobilized GRF2 with the two analytes was verified by fluorescence assays. On-chip tryptic digest assays were then performed on the capture surface and analyzed by microLC-MS/MS. The interaction of GRF2 with calmodulin and Ras was demonstrated, and the lower limit of detection was determined. We also implemented an on-chip immunoprecipitation assay to identify GRF2-binding partners from complex protein mixtures. Cells overexpressing FLAG-GRF2 were lysed and then incubated with the anti-FLAG chip. In addition to detecting GRF2, we also identified calmodulin, demonstrating that this technique can successfully identify endogenous levels of proteins, bound to recombinant bait proteins. This chip-based method has the advantage that no subsequent gel separations of protein complexes prior to LC-MS analysis are required and is therefore amenable to miniaturized high-throughput determination of protein-protein interactions.