Prognostic implications of diagnosing frailty and sarcopenia in vascular surgery practice.

OBJECTIVE: Frailty and sarcopenia are related but independent conditions commonly diagnosed in older patients that can be used to assess their ability to tolerate the stress of major vascular surgery. For surgical decision-making, however, it is important to know the prognostic implications associated with each of these conditions. The study was designed to assess the association of frailty and sarcopenia phenotypes with long-term survival of patients undergoing surgical and nonsurgical management of vascular disease. METHODS: We retrospectively reviewed all patients presenting to the vascular surgery clinic at an academic hospital between December 2015 and August 2017 who underwent prospective frailty assessment with the Clinical Frailty Scale and who had abdominal computed tomography (CT) scans performed within the preceding 12 months. A single axial CT image at the caudal end of the third lumbar vertebra was assessed to measure cross-sectional areas of skeletal muscle. Sarcopenia was defined by established criteria specific for male and female patients. After patients were stratified by frailty and sarcopenia diagnoses along with comorbidities, the association with all-cause mortality was analyzed by Kaplan-Meier curves and Cox regression models. RESULTS: A total of 415 patients underwent both frailty and sarcopenia assessment, of whom 112 (27%) met sarcopenia criteria alone, 48 (12%) met only frailty criteria, and 56 (13%) met criteria for both phenotypes. There were 199 (48%) controls who met neither criterion. Vascular operations were performed in 167 (40%) patients after frailty and sarcopenia assessment, whereas 248 (60%) patients were managed nonoperatively with median (interquartile range) follow-up after CT imaging of 1.5 (1.1-2.2) years. Patients diagnosed with either phenotype were older (mean, 65 years vs 59 years; P < .001) and more likely to be male (69% vs 54%; P < .001) compared with patients without sarcopenia or frailty. Long-term survival was significantly decreased for patients diagnosed with either frailty alone or frailty and sarcopenia who underwent surgical or nonsurgical management (log-rank, P < .001 for both comparisons). In multivariate regression models, however, frailty was the only independent variable (hazard ratio, 7.7; 95% confidence interval, 3.2-18.7; P < .001) that predicted mortality. CONCLUSIONS: Frailty and sarcopenia overlap to varying degrees in patients presenting to vascular surgery clinics and can be used alone or in combination to predict long-term survival of older patients. However, our data indicate that it was only the diagnosis of frailty that was an independent predictor of mortality and had the strongest prognostic significance in patients undergoing both surgical and nonoperative management.

Cationic polymers inhibit the conductance of lysenin channels.

The pore-forming toxin lysenin self-assembles large and stable conductance channels in natural and artificial lipid membranes. The lysenin channels exhibit unique regulation capabilities, which open unexplored possibilities to control the transport of ions and molecules through artificial and natural lipid membranes. Our investigations demonstrate that the positively charged polymers polyethyleneimine and chitosan inhibit the conducting properties of lysenin channels inserted into planar lipid membranes. The preservation of the inhibitory effect following addition of charged polymers on either side of the supporting membrane suggests the presence of multiple binding sites within the channel's structure and a multistep inhibition mechanism that involves binding and trapping. Complete blockage of the binding sites with divalent cations prevents further inhibition in conductance induced by the addition of cationic polymers and supports the hypothesis that the binding sites are identical for both multivalent metal cations and charged polymers. The investigation at the single-channel level has shown distinct complete blockages of each of the inserted channels. These findings reveal key structural characteristics which may provide insight into lysenin's functionality while opening innovative approaches for the development of applications such as transient cell permeabilization and advanced drug delivery systems.